scholarly journals The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis

2021 ◽  
Author(s):  
T. Müller ◽  
M. Demes ◽  
A. Lehn ◽  
J. Köllermann ◽  
S. Vallo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Hpv Infection ◽  
Tumor Type ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Checkpoint Inhibitor Therapy ◽  
Invasive Carcinomas ◽  
Immune Cell Score

Abstract Introduction Penile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias. Materials and methods A cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed. Results Our study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival. Conclusion PD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

scholarly journals Tumor-associated immune cell infiltrate density in penile squamous cell carcinomas

2022 ◽  
Author(s):  
Luca Hladek ◽  
Katrin Bankov ◽  
Jens von der Grün ◽  
Natalie Filmann ◽  
Melanie Demes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell ◽  
Survival Data ◽  
Immune Cell ◽  
Tumor Biology ◽  
Squamous Cell Carcinomas ◽  
Cell Infiltrate ◽  
Advanced Tumor ◽  
Tumor Stages ◽  
Immune Cell Infiltrate

AbstractPenile squamous cell carcinomas are rare tumor entities throughout Europe. Early lymphonodal spread urges for aggressive therapeutic approaches in advanced tumor stages. Therefore, understanding tumor biology and its microenvironment and correlation with known survival data is of substantial interest in order to establish treatment strategies adapted to the individual patient. Fifty-five therapy naïve squamous cell carcinomas, age range between 41 and 85 years with known clinicopathological data, were investigated with the use of tissue microarrays (TMA) regarding the tumor-associated immune cell infiltrate density (ICID). Slides were stained with antibodies against CD3, CD8 and CD20. An image analysis software was applied for evaluation. Data were correlated with clinicopathological characteristics and overall survival. There was a significant increase of ICID in squamous cell carcinomas of the penis in relation to tumor adjacent physiological tissue. Higher CD3-positive ICID was significantly associated with lower tumor stage in our cohort. The ICID was not associated with overall survival. Our data sharpens the view on tumor-associated immune cell infiltrate in penile squamous cell carcinomas with an unbiased digital and automated cell count. Further investigations on the immune cell infiltrate and its prognostic and possible therapeutic impact are needed.

scholarly journals Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 310-316 ◽  
Author(s):  
W. Robert Liu ◽  
Margaret A. Shipp
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Evasion ◽  
Copy Number ◽  
Genetic Basis ◽  
Immune Cell ◽  
Classical Hodgkin Lymphoma ◽  
Copy Number Alterations ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Survival And Growth

Abstract Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

scholarly journals Immune Cell Infiltrate in Chronic-Active Antibody-Mediated Rejection

2020 ◽  
Vol 10 ◽  
Author(s):  
Kasia A. Sablik ◽  
Ekaterina S. Jordanova ◽  
Noelle Pocorni ◽  
Marian C. Clahsen-van Groningen ◽  
Michiel G. H. Betjes
Keyword(s):  
Immune Cell ◽  
Cell Infiltrate ◽  
Antibody Mediated Rejection ◽  
Immune Cell Infiltrate

scholarly journals Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma

Blood ◽  
2017 ◽  
Vol 130 (21) ◽  
pp. 2265-2270 ◽  
Author(s):  
W. Robert Liu ◽  
Margaret A. Shipp
Keyword(s):  
Hodgkin Lymphoma ◽  
Immune Evasion ◽  
Copy Number ◽  
Genetic Basis ◽  
Immune Cell ◽  
Classical Hodgkin Lymphoma ◽  
Copy Number Alterations ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate ◽  
Survival And Growth

Abstract Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.

scholarly journals EPEN-08. A SPATIAL AND PROGNOSTIC ANALYSIS OF IMMUNE CELL INFILTRATE IN PAEDIATRIC EPENDYMOMA

2018 ◽  
Vol 20 (suppl_2) ◽  
pp. i74-i75
Author(s):  
Timothy A Ritzmann ◽  
Francesca Francis ◽  
Sarah-Louise Brudenell ◽  
Hazel A Rogers ◽  
Alex Virasami ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Infiltrate ◽  
Prognostic Analysis ◽  
Immune Cell Infiltrate

scholarly journals The immune cell infiltrate populating meningiomas is composed of mature, antigen-experienced T and B cells

2013 ◽  
Vol 15 (11) ◽  
pp. 1479-1490 ◽  
Author(s):  
L. Fang ◽  
D. E. Lowther ◽  
M. L. Meizlish ◽  
R. C. E. Anderson ◽  
J. N. Bruce ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Cell ◽  
T And B Cells ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate

Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 577-577
Author(s):  
Jason Zhu ◽  
Matthew Labriola ◽  
Sachica Cheris ◽  
Xin Liu ◽  
Kathryn Perkinson ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Immune Cell ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
Tumor Type ◽  
Cell Assays ◽  
Metastatic Urothelial Carcinoma

577 Background: Immune checkpoint inhibitors (ICIs) are now standard of care for mRCC and mUC patients (pts). PD-L1 status is gaining importance as a predictive biomarker, particularly for cisplatin-ineligible mUC. Four different PD-L1 assays vary in thresholds of PD-L1 positivity dependent on tumor type, with limited concordance studies. Given real-world limitations in PD-L1 testing, concordance between assays are needed to distinguish positive (pos)/negative (neg) results and treatment selection. We undertook comparisons of Dako 28–8 and Ventana SP142 assays in mRCC and Dako 22C3 and Ventana SP263 assays in mUC. Methods: 32 patients with mRCC and 18 patients with mUC who had received ICI therapy at Duke Cancer Institute were identified. FFPE archival tumor samples for pts with mRCC were evaluated with Dako 28–8 and Ventana SP142 PD-L1 immunohistochemistry (IHC) assays. For pts with mUC, FFPE archival tumor samples were evaluated with Dako 22C3 and Ventana SP263 PD-L1 IHC assays. Scoring was validated by two pathologists using the scoring system for each assay. PD-L1 status was subsequently correlated to best RECIST response (objective response rate (ORR) defined as stable disease or better)). Results: The majority of mRCC cases (29/32, 91%) were concordant between Dako 28-8 and Ventana SP142 assays (8 cases pos and 21 cases neg), with 3 discordant cases (1 case pos for Dako 28-8 but neg for Ventana SP142 and 2 cases neg for Dako 28-8 but pos for Ventana SP142). The majority of mUC cases (17/18, 94%) were also concordant between Dako 22C3 and Ventana SP263 assays (2 pos cases and 15 neg cases), with 1 indeterminate Dako 22C3 test due to background lymph node. In mRCC, the ORR for PD-L1 pos cases was 45% (5/11) versus 33% (8/24) for PD-L1 neg cases. In mUC, the ORR for PD-L1 positive cases was 50% (1/2) versus 31% (5/16) for PD-L1 neg cases. Conclusions: There was strong concordance between PD-L1 tumor/immune cell assays chosen for comparison in both mRCC and mUC with similar performance characteristics. Although PD-L1 positivity enriches for response to ICIs, many patients respond who are PD-L1 negative. PD-L1 status could be used interchangeably for the majority of cases when selecting treatment in mRCC and mUC.

Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology

2011 ◽  
Vol 115 (3) ◽  
pp. 505-511 ◽  
Author(s):  
Isaac Yang ◽  
Seunggu J. Han ◽  
Michael E. Sughrue ◽  
Tarik Tihan ◽  
Andrew T. Parsa
Keyword(s):  
Pilocytic Astrocytoma ◽  
Immune Cell ◽  
Tumor Biology ◽  
Human Leukocyte ◽  
Low Grade ◽  
High Grade ◽  
Cell Infiltrate ◽  
Leukocyte Antigen ◽  
Pilocytic Astrocytomas ◽  
Immune Cell Infiltrate

Object The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma. Methods Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm2). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen. Results Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma. Conclusions This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

Evaluation of the profile of the immune cell infiltrate in lichen planus, discoid lupus erythematosus, and chronic dermatitis

Pathology ◽  
2008 ◽  
Vol 40 (7) ◽  
pp. 682-693 ◽  
Author(s):  
Mahmoud-Rezk A. Hussein ◽  
Noha M. Aboulhagag ◽  
Hesham S. Atta ◽  
Saad M. Atta
Keyword(s):  
Lichen Planus ◽  
Lupus Erythematosus ◽  
Immune Cell ◽  
Discoid Lupus Erythematosus ◽  
Cell Infiltrate ◽  
Immune Cell Infiltrate

scholarly journals The effect of clozapine and MIS416 on demyelination, remyelination and immunomodulation in the murine cuprizone model

2021 ◽  
Author(s):  
◽  
Nicola Templeton
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Growth Factors ◽  
Immune Cell ◽  
Protective Effects ◽  
Cell Infiltrate ◽  
Motor Impairments ◽  
Immune Cell Infiltrate ◽  
The Central Nervous System ◽  
Improved Performance

<p>Multiple Sclerosis (MS) is a disorder of the central nervous system that affects approximately 2.5 million people worldwide. Due to the heterogeneous nature of the disease, and the want of an identified cause, treatment of MS remains difficult. Treatments are available, however these are limited in efficacy and are not suitable for all forms of MS. Disease pathology is characterised by the formation of demyelinating lesions in the central nervous system (CNS) which lead to cognitive and motor impairments associated with the disease. These CNS lesions can be classified as those with immune cell involvement or those without immune cell infiltrate, which are more commonly seen in progressive forms of MS, and currently, there are no treatments available for progressive MS.  Due to the limited options available for treating progressive MS, this thesis aims to identify the therapeutic effect provided by the immunomodulatory compounds, MIS416 and clozapine, in a non-immune mediated model of MS, which is believed to more closely resemble progressive disease. Both of these compounds have been shown previously to reduce disease burden in an immune-driven animal model of MS. To investigate the effect of immune-modulating therapies on lesions without immune cell infiltrate, the cuprizone model of non-immune demyelination was used.  In summary, the work presented in this thesis found that treatment with MIS416 and clozapine led to improved performance on behavioural assays, although neither agent inhibited cuprizone-induced demyelination or enhanced remyelination. The cellular mechanism behind the observed behavioural improvement is yet to be confirmed. MIS416 was able to maintain its previously identified immunomodulatory properties when administered in this novel setting. Moreover, novel changes to serum growth factors were identified that could provide unexpected benefit to MS patients administered MIS416. In addition to reversing cuprizone-induced behavioural deficits, clozapine reduced LPS-driven inflammatory cytokine production by microglia, indicating that clozapine has the ability to directly reduce inflammation, which may benefit progressive MS patients.   Protective effects provided by either of these compounds could aid in the development of unique combination therapies to target both the inflammatory immune component and the cellular components seen at different stages of MS. MIS416 induced changes to serum cytokines and growth factors in the periphery could be harnessed to treat not just MS but other auto-immune diseases characterised by a similar cytokine profile.</p>

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