A study of the immune infiltrate and patient outcomes in esophageal cancer

2020 ◽  
Author(s):  
Melissa J Conroy ◽  
Susan A Kennedy ◽  
Suzanne L Doyle ◽  
Brian Hayes ◽  
Maria Kavanagh ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Patient Outcomes ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Tissue Microarrays ◽  
Stromal Compartment ◽  
Cancer Subtypes ◽  
Cd8 Cells ◽  
Esophageal Tumors

Abstract Objectives Cancer patient outcomes and selection for novel therapies are heavily influenced by the immune contexture of the tumor microenvironment. Esophageal cancer is associated with poor outcomes. In contrast to colorectal cancer, where the immunoscore is increasingly used in prognostic staging, little is known about the immune cell populations in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC), and their clinical significance. Methods Tissue microarrays were constructed from resected tumor tissue of 72 EAC patients and 23 SCC patients. Immunohistochemical staining of CD3, CD8, CD56, CD68, CD45RO, CD69, IFN-γ, IL-10, IL-4, IL-17, TGF-β, FOXP3 and CD107a was performed. Positivity was examined in both the stromal and epithelial compartments. Statistical analysis was performed to identify differences in immune cell infiltration and functional phenotypes between cancer subtypes and tissue compartments. Results This study identified that esophageal tumors are enriched with CD45RO+ and CD8+ cells and such positivity is significantly higher in SCC compared with EAC. Furthermore, the expression of CD45RO positively correlates with that of CD8 within the tumors of both patient cohorts, suggesting a dominance of memory cytotoxic T cells. This is supported by strong positivity of degranulation marker CD107a in the stromal compartment of EAC and SCC tumors. Cytokine staining revealed a mixed pro- and anti-inflammatory profile within EAC tumors. Conclusions Esophageal tumors are enriched with memory cytotoxic T cells. Applying these measurements to a larger cohort will ascertain the clinical utility of assessing specific lymphocyte infiltrates in EAC and SCC tumors with regards to future immunotherapy use, patient prognosis and outcomes.

747 Evaluation of immune microenvironment of primary lung cancer and synchronous liver metastasis with multispectral imaging system

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A795-A795
Author(s):  
Hyeonbin Cho ◽  
Jae-Hwan Kim ◽  
Ji-Hyun Kim
Keyword(s):  
T Cells ◽  
Liver Metastasis ◽  
Multispectral Imaging ◽  
Immune Cell ◽  
Imaging System ◽  
Cytotoxic T Cells ◽  
Primary Lung Cancer ◽  
Helper T Cells ◽  
Synchronous Liver Metastasis ◽  
Immune Microenvironment

BackgroundCancer immunotherapy (CIT) has substantially improved the survival of cancer patients. However, according to recent studies, liver metastasis was reported to predict worse outcomes for CIT. The main objective of the study is to evaluate the differences in the immune microenvironment (IME) between the primary lung cancer (PL) and synchronous liver metastasis (LM) using a multispectral imaging system.MethodsSix immune markers (CD4, CD8, CTLA-4, granzyme B (GZB), Foxp3 and PD-L1) were analyzed using a multiplex IHC system and inForm program (Akoya) on paired lung-liver samples of 10 patients. Cells were categorized into tumor nest and stroma, and cell counts per unit area were measured for comparison.ResultsThe number of tumor-infiltrating cytotoxic T cells (TIL) in PL (262.5 cells/mm2) was higher than that of LM (113.3 cells/mm2). Additionally, the ratio between the number of TIL and non-TIL was greater in PL (0.31) compared to that of LM (0.26). A similar trend appeared for Helper T cells and regulatory T cells (Treg), as PL consisted of higher numbers of T cells (791.8 Helper T cells/mm2, 195.7 Treg/mm2) than LM (626.3 Helper T cells/mm2, 121.3 Treg/mm2). However, cytotoxic T cells exhibiting GZB+ and CTLA-4- were fewer in PL (140.2 cells/mm2) than in LM (203.3 cells/mm2), and the ratio is 0.69. The mean number of GZB+ TIL in PL (32.5 cells/mm2) was lower than in LM (35.3 cells/mm2), and their proportions among total TIL counts were 0.12 and 0.31, respectively. In PL, GZB+: GZB- ratio is 0.16 while the ratio is 1.91 for LM. A fewer number of TILs exhibiting GZB suggests that PL has lower efficiency in immune response than LM. Another crucial checkpoint receptor that inhibits immune response, CTLA-4, was more prevalent in PL, with CTLA-4+: CTLA-4- ratio in Treg being 0.36 in PL, compared to 0.11 in LM. The tumor proportion score (TPS) of PD-L1 was higher in PL than LM (40.0 vs. 6.6).ConclusionsIn our study, we showed the differences in the numbers of TIL or regulatory T cells and expressions of immune checkpoint receptors (PD-L1, CTLA-4), which significantly influence outcomes for CIT. The study is ongoing to confirm different IME between the PL and LM groups in a larger tumor cohort.ReferencesPeng, Jianhong, et al., Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy. Cancers 2019 Dec; 11(12): 1922. https://doi.org/10.3390/cancers11121922Tumeh, Paul C., et al., Liver Metastasis and treatment outcome with Anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res 2017 May; 5(5): 417–424. doi: 10.1158/2326-6066.CIR-16-0325Parra, E.R., Immune Cell Profiling in Cancer Using Multiplex Immunofluorescence and Digital Analysis Approaches; Streckfus, C.F., Ed.; IntechOpen: London, UK, 2018; pp. 1–13. doi: 10.5772/intechopen.80380Ribas, A., Hu-Lieskovan, S., What does PD-L1 positive or negative mean?. The Journal of Experimental Medicine 2016;213(13):2835–2840. https://doi.org/10.1084/jem.20161462

scholarly journals Diagnostic and pathogenic features of calcifying pseudoneoplasm of the neuraxis

2021 ◽  
Vol 48 (s1) ◽  
pp. S3-S3
Author(s):  
K Yang ◽  
K Reddy ◽  
BH Wang ◽  
A Cenic ◽  
LC Ang ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Cells ◽  
Giant Cells ◽  
List Type ◽  
Neurofilament Protein ◽  
Fibrous Stroma ◽  
Cd8 Cells ◽  
Immunohistochemical Markers ◽  
Spinal Epidural ◽  
Age Range

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumefactive lesion with unclear pathogenesis. It is diagnosed by pathological findings of the typical histological features that include granular amorphous cores with palisading spindle to epithelioid cells, variable fibrous stroma, foreign-body reaction with giant cells, and calcification/ossification occasionally with psammoma bodies. However, its histopathology may be variable and currently immunohistochemistry plays a limited role in its diagnosis and understanding the pathogenesis. In this study, we examined 6 cases of CAPNONs including 3 intracranial and 3 spinal epidural lesions (age range: 59–69 years; 3 males and 3 females). Immunohistochemistry revealed that all CAPNON cores contain abundant positive deposits of neurofilament protein (NFP), which was supported by electron microscopy finding of filaments (8–13 nm in diameter). In comparison, no NFP positivity was found in 5 psammomatous/metaplastic meningiomas or 7 intervertebral tissue lesions with calcification/ossification. In addition, CAPNON cellular areas showed variable numbers of CD8+ cytotoxic T-cells with less CD4+ T-cells and a decreased ratio of CD4/CD8+ cells, versus the intervertebral tissue lesions without CD8+ or CD4+ cells. Our findings suggest that NFP may be a principal constituent of CAPNONs, and thus involved in the pathogenesis of CAPNON. Given the decreased CD4/CD8 ratio, the pathogenic process of CAPNON is possibly immune- mediated.LEARNING OBJECTIVESThe presentation will enable the learner to: 1.Discuss histopathological features of calcifying pseudoneoplasm of the neuraxis (CAPNON) with variation of non-core components.2.Explore diagnostic and pathogenic roles of immunohistochemical markers including neurofilament protein and CD4/CD8 in CAPNON.

Thyroid status regulates tumor microenvironment delineating breast cancer fate

2021 ◽  
Author(s):  
Helena Andrea Sterle ◽  
Ximena Hildebrandt ◽  
Matías Valenzuela Álvarez ◽  
María Alejandra Paulazo ◽  
Luciana Mariel Gutierrez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Lung Metastasis ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Thyroid Status ◽  
Cd8 Cells ◽  
Regulatory T Lymphocytes ◽  
Starting Point

The patient’s hormonal context plays a crucial role in the outcome of cancer. However, the association between thyroid disease and breast cancer risk remains unclear. We evaluated the effect of thyroid status on breast cancer growth and dissemination in an immunocompetent mouse model. For this, hyperthyroid and hypothyroid Balb/c mice were orthotopically inoculated with triple negative breast cancer 4T1 cells. Tumors from hyperthyroid mice showed increased growth rate and an immunosuppressive tumor microenvironment, characterized by increased IL-10 levels and decreased percentage of activated cytotoxic T cells. On the other hand, a delayed tumor growth in hypothyroid animals was associated with increased tumor infiltration of activated CD8+ cells and a high IFNγ/IL-10 ratio. Paradoxically, hypothyroid mice developed a higher number of lung metastasis than hyperthyroid animals. This was related to an increased secretion of tumor CCL2 and an immunosuppressive systemic environment, with increased proportion of regulatory T cells and IL-10 levels in spleens. A lower number of lung metastasis in hyperthyroid mice was related to the reduced presence of mesenchymal stem cells in tumors and metastatic sites. These animals also exhibited decreased percentages of regulatory T lymphocytes and myeloid-derived suppressor cells in spleens, but increased activated CD8+ cells and IFNγ/IL-10 ratio. Therefore, thyroid hormones modulate the cellular and cytokine content of the breast tumor microenvironment. The better understanding of the mechanisms involved in these effects could be a starting point for the discovery of new therapeutic targets for breast cancer.

scholarly journals Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 450 ◽  
Author(s):  
Saeed Daneshmandi ◽  
Barbara Wegiel ◽  
Pankaj Seth
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Lactate Dehydrogenase ◽  
Programmed Cell Death ◽  
Immune Cell ◽  
Cytotoxic T Cells ◽  
Treg Cells ◽  
Interferon Γ ◽  
Mitochondrial Activity ◽  
Small Subset

Immunotherapy is a curable treatment for certain cancers, but it is still only effective in a small subset of patients. We have recently reported that programmed cell death protein-1 (PD-1) ligand (PD-L1) expression is regulated by lactate present at high levels in the tumor microenvironment (TME). We hypothesized that the efficacy of anti-PD-1 treatment can be improved by blocking the lactate-generating enzyme, lactate dehydrogenase-A (LDH-A). Anti-PD-1 treatment of mice harboring LDH-A deficient B16-F10 melanoma tumors led to an increase in anti-tumor immune responses compared to mice implanted with tumors expressing LDH-A. Specifically, we observed heightened infiltration of natural killer (NK) cells and CD8+ cytotoxic T cells in the LDH-A deficient tumors. These infiltrated cytotoxic cells had an elevated production of interferon-γ (IFN-γ) and granzyme B. Mechanistically, CD8+ T cells isolated from the TME of LDH-A deficient B16-F10 melanoma tumors and treated with anti-PD-1 showed enhanced mitochondrial activity and increased reactive oxygen species (ROS) levels. Moreover, infiltration of T regulatory (Treg) cells was diminished in LDH-A deficient tumors treated with anti-PD-1. These altered immune cell profiles were clinically relevant as they were accompanied by significantly reduced tumor growth. Our study suggests that blocking LDH-A in the tumor might improve the efficacy of anti-PD-1 therapy.

scholarly journals Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Niclas C. Blessin ◽  
Ronald Simon ◽  
Martina Kluth ◽  
Kristine Fischer ◽  
Claudia Hube-Magg ◽  
...  
Keyword(s):  
T Cells ◽  
Checkpoint Inhibitors ◽  
Inflammatory Diseases ◽  
Cytotoxic T Cells ◽  
Tissue Microarrays ◽  
Cell Types ◽  
Hashimoto Thyroiditis ◽  
Lung Cancers ◽  
Variable Expression ◽  
Tissue Compartments

TIGIT is an inhibitory immune checkpoint receptor and a putative target for novel immune therapies. Here, we analysed two different types of tissue microarrays of healthy lymphatic and various inflamed tissues, colorectal and lung cancers, as well as >1700 tumour samples from 86 different tumour entities for TIGIT and/or PD-1 by bright field and/or multiplex fluorescence immunohistochemistry. TIGIT was detected in CD8+ cytotoxic T cells, CD4+ T helper cells, FOXP3+ regulatory T cells, and NK cells, but not in CD11c+ dendritic cells, CD68+ macrophages, and CD20+ B lymphocytes. TIGIT expression paralleled that of PD-1. More than 70% of TIGIT+ cells were PD-1+, and more than 90% of the PD-1+ cells were TIGIT+. Expression varied between different tissue compartments. TIGIT expression in tonsil gradually increased from the interfollicular area over the marginal/mantle zone to the germinal centre in all T cell subtypes. In inflammatory diseases, the strongest expression of TIGIT/PD-1 was found in Hashimoto thyroiditis. TIGIT+ lymphocytes were seen in all 86 different tumour entities with considerable high variability of TIGIT positivity within and between different cancer entities. Particularly, high densities of TIGIT+ lymphocytes were, for example, seen in squamous cell cancers of various origins. In summary, the variable expression levels of TIGIT and PD-1 in cell types and tissue compartments illustrate the high complexity of immune microenvironments. The high frequency of TIGIT (and PD-1) expressing lymphocytes in cancers highlights considerable opportunities for cotargeting with checkpoint inhibitors.

scholarly journals Cyclophosphamide Exerts Significant Immunomodulatory Function in Myeloma Patients Treated with Pomalidomide and Dexamethasone

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4482-4482 ◽  
Author(s):  
James Croft ◽  
Andrew Hall ◽  
Katrina Walker ◽  
Amy L Sherborne ◽  
Kevin Boyd ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Research Funding ◽  
Immune Cell ◽  
Cd8 Cells ◽  
Hla Dr ◽  
Trial Treatment ◽  
Equity Ownership ◽  
First Time ◽  
Immune Profiling

Abstract Background and aims Existing evidence regarding the effect of low-dose cyclophosphamide on immune cells in myeloma patients, in particular in combination with the IMiD® compound pomalidomide is limited. We present here for the first time changes in immune cell sub-group composition associated with the addition of cyclophosphamide to pomalidomide in the randomised MUKseven clinical trial. Material and Methods MUKseven is a randomised phase II study for relapsed or refractory myeloma (RRMM) patients comparing cyclophosphamide (500 mg po d1, 15, 21), pomalidomide and dexamethasone (CPd) versus standard pomalidomide and dex (Pd). Patients with ≥2 prior lines of therapy were randomised 1:1 to CPd or Pd and treated until disease progression. All patients underwent bone marrow sampling and peripheral blood collection, the latter for immune cell immunophenotyping at Cycle 1 Day 1 (C1D1; Baseline), C1D14 (on-treatment), C4D14 (on-treatment) and at disease progression. Peripheral blood (PB) T-cell populations were profiled using multicolor flow cytometry (MFC) designed to assess baseline and pharmacodynamic changes in subpopulations including helper, cytotoxic, naïve, memory, and activated/proliferating phenotypes (CD3, CD4, CD8, CD45RA, CD62L, HLA-DR, Ki67. T-cell sub-populations were defined and their respective % of total lymphocyte population used for downstream analyses. Results In total 102 evaluable RRMM patients were randomised, 51 each to CPd and Pd treatment arms, with comparable clinical baseline characteristics. Patients had received a median of 3 prior lines of treatment. Evaluable PB immune profiling data was available for 93 (91%) patients at Baseline, 83 (81%) at C1D14, 55 (54%) at C4D14 and 26 (25%) at progression. We observed trends for changes in baseline T-cell population composition with increasing numbers of prior lines of therapy. Specifically, mean % CD4+ T-cells decreased from 35% for patients with 2 prior lines (n=18) to 30% with 3 (n=33), 23% with 4 and 20% with ≥5 prior lines of treatment (n=27), whilst the % of CD8+ cells were similar, indicating potential differential cumulative effects of anti-myeloma therapy on T-cell populations. We compared changes in T-cell profiles longitudinally over trial treatment from baseline to C1D14 and C4D14 with summary statistics. Overall, there was a marked increase in activated (HLA-DR+) T-cells with therapy, with a 2-fold increase in mean proportion of activated CD4+ and CD8+ from 3.9% and 10.2% at baseline to 7.8% and 19.9% at C1D14 and 7.2% and 28.2% at C4D14, respectively (Figure 1). Trial treatment was associated with a shift in sub-populations within CD8+ T-cells in particular, with a relative % decrease in naïve (CD45RA+) sub-populations and increase in memory (CD45RA-) populations. To identify differences associated with cyclophosphamide treatment a regression analysis was conducted on the C1D14 time point accounting for the treatment a patient received and incorporating their baseline (C1D1) measurement. The mean% estimates for total T-cells (CD3+) at C1D14 were significantly higher for the CPd arm in comparison to Pd: 72.1% [95% CI: 66.5 - 73.6] vs. 64.2% [58.2 - 66.1] (P=0.004). Estimates for the Pd arm appeared similar to baseline [mean C1D1: 61.7%]. Mean% estimates for CD8+ and CD4+ cells were also significantly higher with CPd treatment at C1D14 compared to Pd: 37.2% [32.6 - 38.0] vs. 33.1% [28.5 - 33.7] (P=0.03) and 26.2% [21.6 - 27.0] vs. 21.8% [21.6 - 27.0] (P=0.016), respectively. Importantly, mean% estimates for activated (HLA-DR+) CD4+ cells were significantly higher for the CPd arm 10.1% [6.9 - 9.4] vs 8.1% [5.1 - 7.2] in the Pd arm (P =0.02). There was a trend for additional increase of activated CD8+ cells by addition of cyclophosphamide to Pd therapy (P=0.06). Discussion We demonstrate for the first time in a randomised trial using systematic longitudinal immune profiling that addition of cyclophosphamide to pomalidomide and dexamethasone is significantly associated with altered T-cell profiles and an increased proportion of activated T-cells. MUKseven clinical endpoint data are reported separately, with improved response rates observed for CPd vs. Pd. Correlation of immune profiles with clinical outcomes and tumour genetics will be presented at the conference when PFS outcome data will be mature. Disclosures Boyd: Novartis: Consultancy, Honoraria; Janssen: Honoraria, Other: Travel and Accommodation expenses; Celgene: Consultancy, Honoraria, Other: Advisory role. Garg:Janssen: Honoraria; Novartis: Other: travel support, Research Funding; Takeda: Other: Travel Grant; Amgen: Honoraria, Other: Travel Support. Pawlyn:Janssen: Honoraria, Other: Travel support; Celgene Corporation: Consultancy, Honoraria, Other: Travel support; Amgen: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy, Other: Travel support. Pierceall:Celgene: Employment, Equity Ownership. Cook:Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Seattle Genetics: Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Thakurta:Celgene Corporation: Employment, Equity Ownership. Kaiser:Chugai: Consultancy; Takeda: Consultancy, Other: travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Other: travel support; Amgen: Consultancy, Honoraria.

The impact of neoadjuvant chemotherapy (NACT) on the tumor immune microenvironment (TME) in patients with colorectal cancer with liver metastases (CRCLM).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 124-124
Author(s):  
Medhavi Gupta ◽  
Theresa Smith ◽  
Wiam Bshara ◽  
Julia Terhune ◽  
Kristopher Attwood ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Liver Resection ◽  
Immune Cell ◽  
Cox Regression ◽  
Retrospective Chart Review ◽  
Cancer Society ◽  
Cd8 Cells ◽  
Cellular Density ◽  
The Impact

124 Background: Microsatellite stable (MSS) colorectal cancer and CRCLM are highly resistant to current immunotherapeutic approaches. Understanding the TME and the impact of standard chemotherapeutics is of utmost importance in developing optimal therapeutic strategies. Data is limited on the impact of NACT in the TME. In this study, we sought to explore the effects of chemotherapy on the proportions of different immune cell populations [Total leukohematopoetic cells, CD45+, T cell markers, CD3+, CD8+, and macrophage (M) markers, CD163+, CD68+)], as well as to assess their prognostic capacity. Methods: CRCLM pts who underwent liver resection were divided in 2 groups: pts who had NACT within 4 months of liver resection [NACT (+)] and no NACT [NACT (-)]. Whole slide staining of metastatectomy specimen for CD3, CD8, CD68, CD163, and CD45 was done. Cellular density within representative tumor core sections was analyzed. Retrospective chart review was done to obtain clinical data. Disease free (DFS), relapse free (RFS), and overall survival (OS) were analyzed using Kaplan Meir methods. Association between markers and outcomes was evaluated using Cox Regression Models. Results: A total of 43 pts were studied [NACT (+), n= 14; NACT (-), n=29). There were no significant differences in baseline characteristics between the two groups, including age, primary site, T stage, N stage, and grade. Median OS was 48 months. Outcomes were not significantly different with use of NACT. Within the NACT (+) CRCLM significant increases were seen in densities of CD3, CD8, CD45 and CD163 cells. Densities of CD8 cells were strongly correlated to CD163 cell densities ([r] 0.77, p < .0001). The NACT (+) cohort saw significantly increased ratios of T-cells/macrophages as compared to NACT (-) (CD3/CD68, CD3/CD163, CD8/CD163). High CD45 density was associated with improved OS (HR = 0.28, p = 0.006). CD3, CD8, CD68, and CD163 were not independently associated with OS. However, both the ratio of CD3/CD68 and CD3/163 were associated with improved OS (HR 0.44, p=0.03 and HR 0.27, p=0.03 respectively). Conversely, CD68/45 and CD163/CD45 ratios were associated with a worse OS (HR 1.42, p=0.05 and HR 1.43, p=0.03 respectively). No difference was seen in cellular populations based on the type of NACT received: oxaliplatin vs irinotecan. Conclusions: Our study highlights that the administration of NACT is associated with favorable changes in LM TME. While there is a general increase in leukocytes (CD45), the density of CD3+ and CD8+ T cells is particularly increased. Further, this increase is proportionately greater than the concurrent increases on monocytoid populations, reflected by increased CD3/CD163 and CD8/CD163 ratios. Ratios of T-cells/ macrophages are predictive of survival. This study was partly supported by the American Cancer Society Grant, 126771-IRG-14-194-11-IRG.

The role of cytokines in the immunity development at helminthiasis

2016 ◽  
Vol 3 (4) ◽  
pp. 521-526
Author(s):  
Гришина ◽  
E. Grishina
Keyword(s):  
T Cells ◽  
Defense Mechanism ◽  
Cytotoxic T Cells ◽  
Relationship Building ◽  
Practical Implementation ◽  
Local Immunity ◽  
Effector Cells ◽  
Cd8 Cells ◽  
Protection Mechanisms ◽  
Low Efficiency

Intensive development of the parasitic diseases immunology in the past decade allows making a definite conclusion about the features of the immune response formation in helminthiasis and its key problems, such as short duration, low-efficiency and the ability to cause the development of immunopathological processes. Objective of research: The aim of this review was to identify most significant stages of helminthiasis immunogenesis wich can cause its low protective ability, and for which further comprehensive study of modern molecular biologists, geneticists, biochemists, immunologists and parasitologists should be held to clarify the immunopathology induction mechanisms and improve methods of prophylaxis, diagnosis and treatment of these diseases. Results and discussion. Studies have revealed that the main condition for relationship building in the system “parasite-host” is the presence of protection mechanisms in helminths against exposure to the host’s immune system and immunomodulation mechanisms up to the complete immunosuppression in host. Products of helminths vital activity, so-called secretory-excretory products (SEPs), as well as changed in the process of pathogenesis host proteins and cells become a powerful immune stimulus and activate mechanisms for general and local immunity. The following defense mechanism in helminthiasis is the most effective: participation of IgE antibodies class and IgG2 subclass which play a major role in the activation of cell adhesive activity; influence of cytotoxic T cells (T killer cells, CD8+ -cells); involvement of macrophages, activated with T-cells; work of induced effector cells (eosinophils, neutrophils, mast cells, platelets, etc.), and the results of natural killer (NK) and regulating Treg- lymphocyte population (CD4 + CD25 + -cells) activity. It was shown that helminthiasis is accompanied by oxidative stress, which is characterized by decreased activity of catalase, superoxide dismutase, and an increase of lipid peroxidation products, which may cause primary DNA damage underlying in gene and chromosomal mutations that is shown in prior studies. Parasites metabolites have a cytotoxic effect on somatic, generative and immune cells of host, causing the increase of apoptotic cells among them. Theoretical significance of the data on identification problems of helminthiases immunology is undoubted. Its practical implementation offers the significant increase in the effectiveness of helminthiasis prevention and control.

scholarly journals LGG-22. EVALUATION OF IMMUNE AND GENOMIC CHARACTERISTICS IN PEDIATRIC OPTIC NERVE GLIOMA (ONG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii370-iii370
Author(s):  
Ashley A Campbell ◽  
Andrew M Silverman ◽  
Hanna Moisander-Joyce ◽  
Cheng-Chia Wu ◽  
Mahesh Mansukhani ◽  
...  
Keyword(s):  
T Cells ◽  
Optic Nerve ◽  
Medical Center ◽  
Cytotoxic T Cells ◽  
Additional Patient ◽  
Molecular Characteristics ◽  
Columbia University ◽  
Optic Nerve Glioma ◽  
Cd8 Cells ◽  
Hla Dr

Abstract Pediatric optic nerve glioma (ONG) is a rare, sight-threatening tumor. We previously reported clinical, radiologic, histopathologic, and molecular characteristics of pediatric ONG patients treated at Columbia University Medical Center between 2000–2017. Here we evaluate this cohort and one additional patient using quantitative multiple immunofluorescence (qmIF) and next generation sequencing (NGS) using the Columbia Combined Cancer Panel (CCCP). For qmIF, 4 micron immuno-blank slides were stained for CD3, CD8, CD68, CD163, HLA-DR, and Olig2. QmIF images were analyzed and data were processed in R studio and compared based on tumor mutation and treatment history. QmIF failed in 1 case and CCCP failed in 2 cases. CCCP confirmed KIAA1549:BRAF fusions in 2 patients, identified NF1 in 2 patients, and demonstrated both a KIAA1549:BRAF fusion and SETD2 mutation in the added case. Qualitative analysis showed immune infiltrate across cases included macrophages (CD68+, 1.6–6.5% of all cells) and T cells (CD3+, 0.4% to 1.5%). Non-cytotoxic T cells (CD3+CD8-) comprised 60.7–100% of the T cell compartment. There was no difference when comparing mutation groups. However, patients who previously received radiation had increased CD3+, specifically CD3+CD8- cells compared to non-irradiated patients (p=0.01 and p&lt;0.01, respectively) while CD3+CD8+ and CD68+ cells were not different between groups (p=0.49 and p=0.27, respectively). In summary, qmIF analysis showed increased tumor infiltration by non-cytotoxic T cells in previously irradiated pediatric ONG patients compared to non-irradiated patients, while there was no difference in macrophages of cytotoxic T cells. This type of analysis may be useful in designing immunotherapeutic strategies for pediatric ONG.

scholarly journals Geospatial characterization of immune cell distributions and dynamics across the microenvironment in renal cell carcinoma

2021 ◽  
Author(s):  
Nicholas Chakiryan ◽  
Youngchul Kim ◽  
Anders Berglund ◽  
Gregory Kimmel ◽  
Andrew Chang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Clinical Stage ◽  
Tumor Stroma ◽  
Imaging Analysis ◽  
Cancer Specific Survival ◽  
Stromal Compartment

Abstract We performed multiplex immunofluorescence (mIF) using an array of myeloid and lymphoid markers on primary tumor samples from 122 patients with RCC. Regions of interest (ROIs) were selected from three distinct tumor zones: the tumor-core, stroma, and tumor-stroma interface. Digital pathologic imaging analysis was leveraged to quantify the geospatial location and distribution of immune cells within the TIME, and these findings were correlated with a variety of tumor molecular profiles. For patients with ccRCC, as clinical stage increased, immunosuppressive M2-like CD163+ TAMs migrated from the tumor compartment and into the stroma at the tumor-stroma interface and became increasingly co-localized with CD8+ T-cells. Furthermore, high CD163+ TAM clustering into the stromal compartment and high CD8+/CD163+ stromal co-localization were independently associated with worse OS and cancer-specific survival (CSS), while accounting for clinical stage. Overall, this data suggests that the pro-tumor effect of M2-like TAMs and their effect on CD8+ T-cells may be dependent on their specific geospatial location and distribution within the TIME -- namely, that M2-like TAMs exert their pro-tumor effect and interact with CD8+ T-cells most effectively from the stromal compartment at the tumor-stroma interface.

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