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<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 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 T-cell activation and subset patterns are altered in B-CLL and correlate with the stage of the disease

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 786-792 ◽  
Author(s):  
TH Totterman ◽  
M Carlsson ◽  
B Simonsson ◽  
M Bengtsson ◽  
K Nilsson
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Healthy Subjects ◽  
Lymphocytic Leukemia ◽  
Stage Ii ◽  
T Cell Subsets ◽  
Cd8 Cells ◽  
Hla Dr ◽  
The Absolute

Abstract Two-color FACS analysis was used to study activated and “functional” T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T- suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T- cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.

Characterizing the tumor microenvironment (TME) in primary melanomas using multiplex immunohistochemistry (mIHC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9580-9580
Author(s):  
Robyn Denise Gartrell ◽  
Douglas Kanter Marks ◽  
Thomas Hart ◽  
Edward Stack ◽  
Yan Lu ◽  
...  
Keyword(s):  
Spatial Analysis ◽  
Immune Cell ◽  
Medical Center ◽  
Primary Melanoma ◽  
Columbia University ◽  
Ki67 Expression ◽  
Hla Dr ◽  
Immune Cell Subsets ◽  
Low Levels

9580 Background: Biomarkers are needed in primary melanoma to risk stratify for adjuvant trials. High levels of infiltrating cytotoxic (CD8+) T lymphocytes (CTLs) and low levels of CD68+ macrophages (MΦ) may correlate with prolonged survival but quantification methods are not standardized for clinical practice. HLA-DR is a marker of MΦ activation not expressed by suppressor myeloid cells. A novel pathology technique using mIHC allows for quantitative and spatial analysis of immune cell subsets. Methods: In a pilot set of stage II/III primary melanomas from Columbia University Medical Center (n = 94), clinical follow up is available for 51 cases. 32 had no evidence of recurrence at last follow up (minimum 2 years) while 19 died of melanoma. 5µm slides were stained using Opal multiplexed IHC (mIHC) for DAPI, CD3, CD8, CD68, SOX10, HLA-DR and Ki67. Tumor areas were pre-selected by a dermatopathologist, visualized using Mantra (Perkin Elmer) and analyzed using inForm (Perkin Elmer) and Spotfire (TIBCO). Results: In all patients (n = 94), CTLs are farther from tumor (SOX10+) cells when they are proliferating (Ki67+) (p < 0.0001***), while they are closer to MΦ when they are activated (HLA-DR+) (p = 0.0002***). Next, we evaluated impact on prognosis using disease specific survival (DSS) as an outcome based on median value (n = 51). In this exploratory study no correction for multiple comparisons was made. We find that CTL density correlates with prolonged DSS in tumor (p = 0.0185*) but not in stroma (p = 0.1630 ns). Ratio of density of CD8/CD68+HLA-DR- correlates with DSS in both tumor (p = 0.027*) and stroma (p = 0.017*). Finally, distance from CTLs to HLA-DR- MΦ was significantly greater in non-recurrent melanomas as compared to recurrent ones (p = 0.0167*). Conclusions: HLA-DR expression on MΦ and Ki67 expression on tumor cells correlate with position of CTLs in TME in primary melanoma. CTL density is a favorable prognostic marker while HLA-DR non-expressing MΦ may favor tumor progression. Quantitative mIHC allows for accurate spatial analysis of immune subsets within the TME and the development of novel, more accurate and potentially clinically relevant biomarkers.

scholarly journals Increased CD69 and Human Leukocyte Antigen-DR Expression on T Lymphocytes in Insulin-Dependent Diabetes Mellitus of Long Standing

1998 ◽  
Vol 83 (6) ◽  
pp. 2204-2209 ◽  
Author(s):  
Alois Gessl ◽  
Werner Waldhäusl
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
Human Leukocyte ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Cd4 Cells ◽  
Cd8 Cells ◽  
Leukocyte Antigen ◽  
Hla Dr ◽  
Insulin Dependent

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n= 31; median age ± sd,, 28 ± 6.9 yr) and of long standing (DML; n = 27; age, 33 ± 10.4 yr; median duration of disease, 105 months), CD4+ and CD8+ T cells were analyzed to determine their naive and memory subsets as well as their expression of human leukocyte antigen (HLA)-DR, interleukin-2 receptor α-chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 ± 8.2 yr) served as controls. No deviation was seen in either IDDM group compared to HS in CD25 expression on CD4+ or CD8+ cells or in their CD45RA+ or CD45RA− subsets. HLA-DR expression, however, was increased (P &lt; 0.05) in total CD8+ cells and CD45RA+ cells, with CD45RA− CD8+ cells joining the prevailing pattern only in DML. Among CD4+ cells, increased expression of HLA-DR molecules was restricted to total and CD45RA− cells in DML. CD69 expression did not differ between IDDM and HS, but differed between DML (CD4+, CD8+, and CD45RA− CD4+) and DM only. In conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to memory cells (CD45RA−) among CD4+ cells in DML and is more markedly confined to naive (CD45RA+) than to memory CD8+ cells, whereas the early activation antigen CD69 is more readily expressed in DML than in DM. The observed activation of circulating T cells suggests an ongoing immune process in IDDM both at clinical manifestation and after long duration.

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.

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.

Immune profiling of circulating T cells and TILs following neoadjuvant ipilimumab and chemotherapy in non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 26-26
Author(s):  
John Yi ◽  
Jeffrey Melson Clarke ◽  
Patrick Healy ◽  
Xiaofei F. Wang ◽  
Debra Shoemaker ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Objective Response ◽  
Study Objective ◽  
Cd8 Cells ◽  
Hla Dr ◽  
Circulating T Cells ◽  
Immune Profiling

26 Background: Ipilimumab (Ipi) is a humanized CTLA-4 antibody that blocks binding of CTLA-4 to B7, permitting T cell activation through CD28. Phased in Ipi added to chemotherapy (C) may enhance efficacy in NSCLC. Methods: Patients with stage 2 or 3A NSCLC received neoadjuvant carboplatin AUC6 plus paclitaxel 200 mg/m2 every 21 days for 3 cycles and Ipi (10 mg/kg) was given on day 1 for cycles 2 and 3. Blood for immune profiling of circulating T cells was collected at baseline, after chemotherapy alone, and after chemotherapy plus Ipi. Tumor infiltrating lymphocytes (TIL) were derived from 7 available tumors. Polychromatic flow cytometry (PFC) analyses were performed on peripheral blood mononuclear cells (PBMC) and TIL. Objective response rates were assessed according to RECIST 1.1 criteria. Results: Of the 24 patients enrolled on this study, objective responses after 3 cycles of neoadjuvant C plus ipi included 2 PD, 8 SD, and 14 PR. Phenotypic analyses revealed that PBMC from all 24 patients were highly activated following two cycles of Ipi (cycle 3) as evidenced by significantly increased frequencies of CD28, ICOS, HLA-DR, PD-1, and CTLA-4 expressing CD4+ cells; and ICOS, HLA-DR, and CTLA-4 expressing CD8+ cells. The frequencies of Tregs were highly variable among the 24 participants. Two of the 24 participants had levels of MDSC cells above 15%. TIL contained far greater frequencies of activated CD4+ and CD8+ cells than found in the PBMC at cycle 3. Tumor associated antigen (TAA)-specific CD4+ or CD8+ cells were detected at baseline in 4 patients (24%), but their relative frequencies remained unaltered by Ipi therapy. No patients developed detectable de novo TAA reactivities while on Ipi therapy. Conclusions: Combined neoadjuvant Ipi plus chemotherapy produced significantly increased frequencies of highly activated CD4+ and CD8+ populations in the peripheral blood and the tumor microenvironment. TAA-specific CD4+ or CD8+ cells were detected in PBMC at baseline in a subset of patients. No TAA-reactive T cells were detected among the 7 TIL samples analyzed. Analysis for predictive or pharmacodynamic biomarkers is ongoing. Clinical trial information: NCT01820754.

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 Peripheral innate and adaptive immune cells during COVID-19: Functional neutrophils, pro-inflammatory monocytes and half-dead lymphocytes

2020 ◽  
Author(s):  
Emel Eksioglu-Demiralp ◽  
Servet Alan ◽  
Uluhan Sili ◽  
Dilek Bakan ◽  
Ilhan Ocak ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Absolute Number ◽  
Innate Immune ◽  
Cd8 Cells ◽  
Adaptive Immune ◽  
Inflammatory Monocytes ◽  
Adaptive Immune Cells ◽  
Hla Dr

A better understanding of the innate and adaptive cells in the COVID-19 disease caused by the SARS-CoV-2 coronavirus is a necessity for the development of effective treatment methods and vaccines. We studied phenotypic features of innate and adaptive immune cells, oxidative burst, phagocytosis and apoptosis. One hundred and three patients with COVID-19 grouped according to their clinical features as mild (35%), moderate (40.8%), and severe (24.3%) were included in the study. Monocytes from all COVID-19 patients were CD16+ pro-inflammatory monocytes. Neutrophils were mature and functional. No defect has been found in ROS production of monocytes and neutrophils as well as no defect in their apoptosis. As bridging cells of the innate and adaptive immune system; the percentage of NK cells was in normal range whereas the percentages of CD3-CD8+CD56+ innate lymphoid and CD3+CD56+ NK like T cells were found to be high in the severe cases of COVID-19. Although absolute numbers of all lymphocyte subsets were low and showed a tendency for a gradual decrease in accord with the disease progression, in all COVID-19 patients, the lymphocyte subset with the most decreased absolute number was B lymphocytes, followed by CD4 + T cells in the severe cases. The percentages of suppressive, CD3+CD4-CD8-; HLA-DR+CD3+ and CD28-CD8+ cells were found to be significantly increased. Importantly, we demonstrated spontaneous caspase-3 activation and increased lymphocyte apoptosis. Altogether our data suggest that SARS-CoV- 2 primarily affects lymphocytes not innate cells. So that, it may interrupt the cross-talk between adaptive and innate immune systems.

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