scholarly journals PD-L1 Expression and a High Tumor Infiltrate of CD8+ Lymphocytes Predict Outcome in Patients with Oropharyngeal Squamous Cells Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5228 ◽  
Author(s):  
Nora Wuerdemann ◽  
Sibel E. Gültekin ◽  
Katharina Pütz ◽  
Claus Wittekindt ◽  
Christian U. Huebbers ◽  
...  
Keyword(s):  
Immune Escape ◽  
Statistical Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Mhc I ◽  
Hpv Dna ◽  
Squamous Cells ◽  
Hpv Status ◽  
Tumor Infiltrate ◽  
Infiltrating Lymphocytes

Carcinogenesis of human papillomavirus (HPV)-related (+) oropharyngeal squamous cell carcinoma (OPSCC) differs from HPV-negative (–) OPSCC. HPV-related immune-escape-mechanism could be responsible for the development and progression of HPV+ tumors and an immunophenotype different from HPV– OPSCC is expected. The purpose of this study was to analyze the expression of programmed cell death protein 1 ligand 1 (PD-L1) and its prognostic relevance in relation to CD8+ tumor infiltrating lymphocytes (TILs) and the major histocompatibility complex (MHC) I expression in OPSCC. We quantified PD-L1 expression on tumor cells (TC) and macrophages and MHC I expression in association to CD8+ TILs by immunohistochemistry on tissue microarray derived from 171 HPV+/-OPSCC. HPV-status was determined by p16INK4a immunohistochemistry/HPV-DNA detection. Presence of CD8+ TILs, PD-L1 expression on TC, and a more frequent loss of MHC I in HPV+ compared to HPV- OPSCC was detected. A high amount of CD8+ TILs in the whole cohort and in HPV+ OPSCC and PD-L1 expression on TC in HPV- OPSCC was associated with favorable overall survival. There was a trend for an improved outcome according to PD-L1 expression (macrophages) in HPV+ OPSCC without reaching statistical significance. CD8+ TILs and PD-L1-expression have prognostic impact in OPSCC and might present useful biomarkers for predicting clinical outcome and personalized therapy concepts.

Prognostic impact of tumor-infiltrating lymphocytes (TIL's) and stromal-infiltrating lymphocytes (SIL's) in triple-negative breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 83-83
Author(s):  
Santiago Sherwell-Cabello ◽  
Antonio Maffuz-Aziz ◽  
Diego A Camacho-Ramírez ◽  
Verónica Bautista-Piña ◽  
Nina P Ríos-Luna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Advanced Stages ◽  
Infiltrating Lymphocytes

83 Background: Immune response seems to improve outcome in women with Triple-Negative Breast Cancer (TNBC). Recent data suggests that the presence of Tumor-Infiltrating Lymphocytes is an independent factor associated with better prognosis. In this study, we evaluate the prognostic impact of both TIL´s and SIL´s in patients with TNBC. Methods: Data on women diagnosed with TNBC between 2005 and 2013, was collected by retrospectively reviewing at our institute. The rate of intratumoral and/or stromal lymphocytes was evaluated in all hematoxylin and eosin-stained histopathologic sections according to Denkert et al. The five-year disease-free survival (DFS) and overall survival (OS) were compared between groups with the presence or absence of TIL´s or SIL´s. Demographic and clinical characteristics were assessed, variables with a statistical significance between groups were analyzed in a multivariate analysis. Results: A total of 172 patients with TNBC treated at this institution were included with a mean age of 49.8 years. A complete absence of tumor lymphocytes was found in 88 patients while the presence of intratumoral, stromal or both was found in 84 (48.8%). A mean follow-up of 46.12 months showed significantly higher rates of both DFS and OS in women with SIL´s and TIL´s (p = 0.014 and 0.042 respectively) in locally advanced stages (LAS), regardless the rate of infiltrating lymphocytes found [Table 1]. SIL´s are correlated with a better prognosis compared with TIL´s (p = 0.028 and 0.091 respectively). Non-significant differences were found in early stages (p= 0.255). Conclusions: These results show that the presence of SIL´s or TIL´s are strongly associated with higher rates of DFS and OS in LAS, especially when SIL´s are found, suggesting that immunity seems to play a key role regarding the outcome in women with TNBC. Independent of the rate of lymphocytic infiltrate, its presence has a statistical significance. Because it is a feasible and inexpensive test that can be used as a prognostic predictor, we suggest assessing both SIL's and TIL's in histopathologic biopsies of patients with TNBC. [Table: see text]

scholarly journals Prognostic Significance of Tumor-Infiltrating Lymphocytes in Oropharyngeal Cancer

2007 ◽  
Vol 86 (8) ◽  
pp. 506-511 ◽  
Author(s):  
Samer Rajjoub ◽  
Suzanne R. Basha ◽  
Eugene Einhorn ◽  
Marc C. Cohen ◽  
Doug M. Marvel ◽  
...  
Keyword(s):  
Oropharyngeal Cancer ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Samples ◽  
Human Papillomavirus Type 16 ◽  
Large Numbers ◽  
Hpv Status ◽  
Infiltrating Lymphocytes

The presence of tumor-infiltrating lymphocytes has been shown to significantly improve clinical outcomes in many types of cancer. However, their effects on outcomes in patients with oropharyngeal cancer specifically have yet to be elucidated. We conducted a retrospective study in an effort to shed light on this issue. We reviewed the records of 48 consecutively presenting patients with oropharyngeal cancer, and we performed immunohistochemistry to analyze their archived paraffin-embedded tissue samples for the presence of CD3-positive tumor-infiltrating lymphocytes. We also used real-time polymerase chain reaction testing to look for human papillomavirus type 16 (HPV-16) in the tumors. We found that patients with large numbers of tumor-infiltrating lymphocytes (CD3high) had a significantly lower incidence of metastasis at presentation than did those with low numbers of tumor-infiltrating lymphocytes (CD3low) (40.0 vs. 88.5%; p = 0.001), regardless of HPV status. When HPV status was taken into account, the correlation between a high CD3 count and a lower rate of metastasis was maintained in the HPV-positive patients but not in the HPV-negative patients. We also found that the CD3high patients had higher rates of overall survival and disease-free survival at 3 and 5 years than did the CD3low patients; however, these differences only approached but did not reach statistical significance.

Prognostic impact of tumor-infiltrating lymphocytes in non-small cell lung carcinomas

2021 ◽  
pp. 021849232110421
Author(s):  
Mona Mlika ◽  
Ayoub Saidi ◽  
Nesrine Mejri ◽  
Mehdi Abdennadher ◽  
Chokri Haddouchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Lung Carcinomas ◽  
Forkhead Box ◽  
Infiltrating Lymphocytes

Introduction Tumor-infiltrating lymphocytes represent a pivotal component of the host anti-tumor response. Thus, they considerably influence the evolution of cancers including non-small cell lung carcinomas. Even if, this important role is consensual, many discordant results are published in the literature about the prognostic role of the different populations of tumor-infiltrating lymphocytes. The aim of our work was to evaluate the prognostic impact of CD8+, CD4+, and forkhead box protein P3+ lymphocytes in the tumor microenvironment of non-small cell lung carcinomas. Methods We conducted a retrospective descriptive study, which included non-small cell lung carcinomas diagnosed in the department of pathology and followed in the medical oncology department of the same hospital between 2011 and 2015. Tumor-infiltrating lymphocytes were analyzed by the immunohistochemical method for forkhead box protein P3, CD4, and CD8. Intratumoral and stromal-labeled lymphocytes were quantified by manual counting at high magnification (×400). Forkhead box protein P3+/CD8+, forkhead box protein P3+/CD4+, and CD8+/CD4+ ratios were subsequently calculated. The prognostic value of tumor-infiltrating lymphocytes was assessed in respect of overall survival, recurrence-free survival, and relapse-free survival. Results Thirty-nine patients were included. The mean age of patients was 59.6 years. A complete surgical resection ( p = 0.009), and a CD8/CD4 ratio ( p = 0.008) were prognostic factors for overall survival. Complete surgical resection ( p = 0.003), the forkhead box protein P3/CD8 ( p = 0.005), and forkhead box protein P3/CD4 ( p = 0.037) ratios were prognostic factors for recurrence-free survival. The CD8+ tumor-infiltrating lymphocytes rate ( p = 0.037) was a prognostic factor for relapse-free survival with a threshold of 67.8/high power field. Microscopic subtype ( p = 0.037) was a prognostic factor for relapse-free survival when only adenocarcinoma and squamous cell carcinoma were considered. In multivariate analysis, age ( p = 0.004) and a CD8/CD4 ratio ( p = 0.016) were independent predictors of overall survival. Conclusion Despite the limitations of our study, our results confirm the prognostic value of tumor-infiltrating lymphocytes in non-small cell lung carcinomas and the importance of the combined quantification of their different subpopulations.

scholarly journals Clinical Impact of Tumor-Infiltrating Lymphocytes and PD-L1-Positive Cells as Prognostic and Predictive Biomarkers in Urological Malignancies and Retroperitoneal Sarcoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3153
Author(s):  
Makito Miyake ◽  
Shunta Hori ◽  
Takuya Owari ◽  
Yuki Oda ◽  
Yoshihiro Tatsumi ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Tumor Infiltrating Lymphocytes ◽  
Retroperitoneal Sarcoma ◽  
Prognostic Impact ◽  
Lymphocyte Migration ◽  
Primary Tumors ◽  
Urological Malignancies ◽  
Infiltrating Lymphocytes ◽  
Shed Light

Over the past decade, an “immunotherapy tsunami”, more specifically that involving immune checkpoint inhibitors (ICIs), has overtaken the oncological field. The interaction and cross-talk among tumor cells and several immune cells in the tumor microenvironment are dynamic and complex processes. As immune contexture can vary widely across different types of primary tumors and tumor microenvironments, there is still a significant lack of clinically available definitive biomarkers to predict patient response to ICIs, especially in urogenital malignancies. An increasing body of evidence evaluating urological malignancies has proven that tumor-infiltrating lymphocytes (TILs) are a double-edged sword in cancer. There is an urgent need to shed light on the functional heterogeneity in the tumor-infiltrating immune system and to explore its prognostic impact following surgery and other treatments. Notably, we emphasized the difference in the immunological profile among urothelial carcinomas arising from different primary origins, the bladder, renal pelvis, and ureter. Significant differences in the density of FOXP3-positive TILs, CD204-positive tumor-infiltrating macrophages, PD-L1-positive cells, and colony-stimulating factors were observed. This review discusses two topics: (i) the prognostic impact of TILs and (ii) predictive biomarkers for ICIs, to shed light on lymphocyte migration in four solid tumors, the urothelial carcinoma, renal cell carcinoma, prostate cancer, and retroperitoneal sarcoma.

Intraepithelial CD94+ tumor-infiltrating lymphocytes in a context of HLA-E overexpression as a new immune checkpoint to predict prognosis in colorectal carcinomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14592-e14592
Author(s):  
Celine Bossard ◽  
Juliette Eugene ◽  
Nicolas Jouand ◽  
Delphine Dansette ◽  
Edouard Leveque ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Tumor Infiltrating Lymphocytes ◽  
High Density ◽  
Point Of View ◽  
Mhc Class Ib ◽  
Immune Resistance ◽  
Infiltrating Lymphocytes ◽  
Inhibitory Immune Checkpoint

e14592 Background: A better understanding of the immune-modulating interactions between tumor cells and immune cells underlying the balance between immune control and immune resistance in colorectal cancer (CRC) is crucial for the design of immunotherapies. We have previously demonstrated that overexpression of the human MHC class Ib molecule - HLA-E/β2 microglobulin - by tumor cells in CRC was associated with an unfavorable prognosis, suggesting its involvement in immune escape. However, the specific receptor of HLA-E/β2m - CD94/NKG2A, inhibitory or CD94/NKG2C, activating - expressed by tumor-infiltrating lymphocytes (TIL), as well as the influence of the microsatellite status in HLA-E/β2m overexpression, remain unknown. Methods: We investigated in the primary tumor of 245 CRC patients 1) the association of HLA-E/β2m overexpression and the density of CD94+ intraepithelial TIL (IEL-TIL) with the microsatellite status, 2) the nature of CD94+ TIL and the receptor expressed - CD94/NKG2A or CD94/NKG2C - and 3) the prognostic influence of CD94+ IEL-TIL. Results: HLA-E/β2m was preferentially overexpressed in MSI compared with MSS CRC (44,6 % vs 18,4 % respectively, p = 0.0001), and significantly associated with a high density of CD94+ IEL-TIL in MSI (0,9% in HLA-E/β2m+ vs 0,2% in HLA-E/β2m– CRC, p = 0,001), and in MSS CRC (0,38% vs 0,15%, p < 0,0001). These CD94+ TIL mostly corresponded to CD8+ αβ T cells preferentially expressing the inhibitory NKG2A chain. Finally, a high density of CD94+ IEL-TIL was independently associated with a worse OS (p = 0.03). Conclusions: These results strongly suggest that HLA-E/β2m - CD94/NKG2A interactions, preferentially up-regulated in MSI CRC, represent a promising inhibitory immune checkpoint. From a clinical point of view, this inhibitory immune checkpoint could be blocked by the new anti-NKG2A monoclonal antibody.

scholarly journals PUB038 Prognostic Impact of FOXP3-Positive Tumor Infiltrating Lymphocytes in Small-Cell Lung Cancers

2017 ◽  
Vol 12 (11) ◽  
pp. S2377-S2378
Author(s):  
L. Bonanno ◽  
A. Pavan ◽  
M.V. Dieci ◽  
M. Fassan ◽  
E. Di Liso ◽  
...  
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Prognostic Impact ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Infiltrating Lymphocytes
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