scholarly journals High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

2020 ◽  
Author(s):  
Jiangyong Liu ◽  
Mingming Gu ◽  
Yang Xue ◽  
Yong Ren ◽  
Wencai Huang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Good Prognosis ◽  
High Expression ◽  
Quantitative Immunofluorescence ◽  
L1 Protein ◽  
Infiltrating Lymphocytes

Abstract Objective Solitary cavitary lung cancer is one of the rare types of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma and immunotherapy remains unknown. We aimed to assess programmed cell death ligand-1(PD-L1) expression and CD8-positive (CD8+) tumor infiltrating lymphocytes (TILs) density, and evaluate their prognostic significance of patients with cavitary lung adenocarcinoma (LUAD). Methods 65 patients diagnosed as solitary cavitary LUAD were included in this study, 30 cases of noncavitary LUAD patients were collected as controls, and their specimens from surgery or biopsy were obtained. Expression of PD-L1 protein and CD8+ TILs were detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlations of PD-L1 expression and clinicopathological features, including overall survival in cavitary LUAD patients was evaluated based on the follow-up data. Results Overexpression of PD-L1 protein was detected in the tumor tissues of cavitary LUAD patients compared to the noncavitary LUAD controls. PD-L1 expression level was significantly related to the lymph node (P = 0.001), TNM stage (P = 0.024), and CD8+ TIL status (rs= -0.272, P = 0.025). High PD-L1 expression predicted high mortality rate (P < 0.001), but CD8+ TIL group showed better survival in cavitary LUAD patients (P = 0.011). This phenotype with high PD-L1 expression and low CD8 + TIL predicted poorer overall survival of the patients with cavitary LUAD, compared to the other phenotypes. Moreover, CD8+ TIL was an independent good prognosis factor. Conclusion We firstly demonstrated that PD-L1 is upregulated in the cavitary LUAD patients, and high expression of PD-L1 negatively correlated with CD8 T cell infiltrating status. High PD-L1 expression and low CD8 + TIL can predict poorer overall survival of the patients with cavitary LUAD.

scholarly journals PD-1, PD-L1 Protein Expression in Non-Small Cell Lung Cancer and Their Relationship with Tumor-Infiltrating Lymphocytes

2017 ◽  
Vol 23 ◽  
pp. 1208-1216 ◽  
Author(s):  
Yayi He ◽  
Leslie Rozeboom ◽  
Christopher J. Rivard ◽  
Kim Ellison ◽  
Rafał Dziadziuszko ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Small Cell Lung ◽  
L1 Protein ◽  
Infiltrating Lymphocytes

scholarly journals Impact of PD-L1 and PD-1 Expression on the Prognostic Significance of CD8+ Tumor-Infiltrating Lymphocytes in Non-Small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Enrico Munari ◽  
Marcella Marconi ◽  
Giulia Querzoli ◽  
Gianluigi Lunardi ◽  
Pietro Bertoglio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Infiltrating Lymphocytes

The immune infiltrate within tumors has proved to be very powerful in the prognostic stratification of patients and much attention is also being paid towards its predictive value. In this work we therefore aimed at clarifying the significance and impact of PD-L1 and PD-1 expression on the prognostic value of CD8+ tumor infiltrating lymphocytes (TILs) in a cohort of consecutive patients with primary resected non-small cell lung cancer (NSCLC). Tissue microarrays (TMA) were built using one representative formalin fixed paraffin embedded block for every case, with 5 cores for each block. TMA sections were stained with PD-L1 (clone SP263), PD-1 (clone NAT105) and CD8 (clone SP57). Number of CD8+ cells per mm2 were automatically counted; median, 25th and 75th percentiles of CD8+ cells were used as threshold for statistical clinical outcome analysis and evaluated in patients subgroups defined by expression of PD-L1 and PD-1 within tumors. We found an overall strong prognostic value of CD8+ cells in our cohort of 314 resected NSCLC, especially in PD-L1 negative tumors lacking PD-1+ TILs, and demonstrated that in PD-L1 positive tumors a higher density of CD8+ lymphocytes is necessary to improve the prognosis. Our data strengthen the concept of the importance of the assessment and quantification of the immune contexture in cancer and, similarly to what has been carried on in colorectal cancer, promote the efforts for the establishment of an Immunoscore for NSCLC for prognostic and possibly predictive purposes.

Expression of immune response markers in Arab patients with lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21543-e21543
Author(s):  
Abdul Rahman Jazieh ◽  
Adda Bounedjar ◽  
Hanaa Bamefleh ◽  
Turki Al-Fayea ◽  
Hatim Q. Almaghraby ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
High Expression ◽  
P Value ◽  
Arab Population ◽  
Cd8 Cells ◽  
Immuno Histochemistry ◽  
Infiltrating Lymphocytes

e21543 Background: Programmed death-ligand 1 (PD-L1) is a marker for checkpoint inhibitors use in management of solid tumor especially non-small cell lung cancer (NSCLC). Our study aimed at determining the patterns of PD-L1 expression and CD8 immunostains in patients with NSCLC in Arab population. Methods: Archival tumor tissue form patients with confirmed diagnosis of NCSLC were obtained and stained for PD-L1 using antibody 22C3 by Dako using Immuno-histochemistry stain (IHC) and giving Tumor Proportion Score (TPS) a percentage number from 0 to 100% of stained tumor cells. Tumors were categorized into negative expressers (TPS<1%), low positive (TPS 1-49%), and high positive (TPS 50% -100%). Correlation of expression with clinical and pathological features including CD8+ lymphocyte density was analyzed. Results: Two hundred NSCLC cases were included in the study from 6 centers in Saudi Arabia and Algeria. Median age was 65 years (28-93) and majority were males (75%) with stage 4 NSCLC (64%). The TPS was high in 37 patients (18%), low in 60 patients (30%), and negative in 103 patients (52%). In a univariate analysis, the following were significant predictors of any PD-L1 expression (>1%): male gender, being Saudi national patients, high expression of CD8+ and the presence of tumor infiltrating lymphocytes. In the multivariate analysis, only high expression of CD8+ cells (>2+) was significant with Odd Ratio (OR) of 4.4 (95% Confidence interval 1.5-12.9, p value of 0.003). Conclusions: PD-L1 expression in our population is similar to the published literature and correlated with the density of CD8+ cells. Validation of the predictive value of this marker in our population and identifying easier and reliable methods to test for it is warranted.

The integration of proportion and cell counts of stromal, not intratumoral, PD-1+ tumor-infiltrating lymphocytes has prognostic significance in esophageal squamous cell carcinoma

2020 ◽  
Author(s):  
Qingkun Song ◽  
Feng Shi ◽  
Shuo Xiao ◽  
Yuchen Li ◽  
Yanjie Zhao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
High Power Field ◽  
Prognostic Effect ◽  
Cell Counts ◽  
Infiltrating Lymphocytes

Summary The present study aimed to investigate the prognostic effect of intratumoral and stromal exhausted tumor-infiltrating lymphocytes (TILs) on operable esophageal cancer patients. We performed a retrospective cohort study by consecutively recruiting 142 patients with esophageal cancer. The proportion and cell counts of intratumoral and stromal PD-1+ TILs in tumor microenvironment were independently evaluated by two pathologists. Neither proportion nor cell counts of intratumoral PD-1+ TILs was associated with prognosis (p &gt; 0.05). However, patients with the proportion of stromal PD1+ TILs &gt;20% had the median overall survival (OS) at 19 months, significantly longer than those with the proportion = 20%. The adjusted hazard ratio (HR) was 1.49 (95%CI 0.82, 2.69). Patients with cell counts of stromal PD1+ TILs = 18/ high-power field (HPF) had the median disease-free survival (DFS) at 10 months. However, patients with cell counts&gt;18/HPF had the median DFS at 48 months (p = 0.037), and the adjusted HR was 0.59 (95%CI 0.35, 1.01). Compared with patients with proportion = 20% and cell counts &gt;18/HPF of stromal PD1+ TILs, patients with proportion = 20% and cell counts = 18/HPF, proportion &gt;20% and cell counts &gt;18/HPF, and proportion &gt;20% and cell counts = 18/HPF, had the adjusted HRs increased to 3.73, 3.36 and 3.99 for DFS (p for trend being 0.030) and the adjusted HRs increased to 2.95, 3.64 and 3.82 (p for trend being 0.015) for OS, respectively. The integration of proportion and cell counts of PD-1+ stromal TILs has a significant association with the relapse and overall survival of esophageal cancer patients. Further prospective studies are warranted.

scholarly journals Expression of Immune Response Markers in Arab Patients With Lung Cancer

2020 ◽  
pp. 1218-1224
Author(s):  
Abdul Rahman Jazieh ◽  
Adda Bounedjar ◽  
Hanaa Bamefleh ◽  
Turki Alfayea ◽  
Hatim Q. Almaghraby ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
High Expression ◽  
Arab Population ◽  
Cd8 Cells ◽  
Programmed Death ◽  
Pathologic Features ◽  
Cluster Of Differentiation ◽  
Infiltrating Lymphocytes

PURPOSE Programmed death-ligand 1 (PD-L1) is a marker for checkpoint inhibitor use in the management of solid tumors, especially in non–small-cell lung cancer (NSCLC). Our study was aimed at determining the patterns of PD-L1 expression and cluster of differentiation 8 (CD8) immunostains in patients with NSCLC in the Arab population. METHODS Archival tumor tissue from patients with a confirmed diagnosis of NSCLC were obtained and stained for PD-L1 with antibody 22C3, using immunohistochemistry staining and giving the tumor proportion score (TPS) as a percentage from 0%-100% of stained tumor cells. Tumors were categorized into negative expressers (TPS < 1%), low positive (TPS, 1%-49%), and high positive (TPS, 50%-100%). Correlation of expression with clinical and pathologic features, including CD8-positive (CD8+) lymphocyte density, was also analyzed. RESULTS Two hundred patients with NSCLC were included in the study from 6 centers in Saudi Arabia and Algeria. Median age was 65 years (28-93 years), and the majority were men (75%) with stage 4 NSCLC (64%). The TPS was high in 37 patients (18%), low in 60 patients (30%), and negative in 103 patients (52%). In a univariate analysis, the following were significant predictors of any PD-L1 expression (> 1%): male sex, being Saudi national patients, high expression of CD8+, and presence of tumor-infiltrating lymphocytes. In the multivariate analysis, only high expression of CD8+ cells (≥ 2+) was significant, with an odds ratio of 4.4 (95% CI, 1.5 to 12.9; P = .003) CONCLUSION PD-L1 expression in our population is similar to the published literature and correlated with the density of CD8+ cells. Validation of the predictive value of this marker in our population and identifying easier and reliable methods to test for it are warranted.

scholarly journals Overexpression of an Immune Checkpoint (CD155) in Breast Cancer Associated with Prognostic Significance and Exhausted Tumor-Infiltrating Lymphocytes: A Cohort Study

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Yu-Chen Li ◽  
Quan Zhou ◽  
Qing-Kun Song ◽  
Rui-Bin Wang ◽  
Shuzhen Lyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cohort Study ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Microenvironment ◽  
Infiltrating Lymphocytes ◽  
Low Expression

Purpose. The immune checkpoint inhibitor is approved for breast cancer treatment, but the low expression of PD-L1 limits the immunotherapy. CD155 is another immune checkpoint protein in cancers and interacts with ligands to regulate immune microenvironment. This study is aimed at investigating the expression of CD155 and the association with prognosis and pathological features of breast cancer. Methods. 126 patients were recruited this cohort study consecutively, and CD155 expression on tumor cells was detected by immunohistochemistry. The Kaplan-Meier survival curve and Cox hazard regression model were used to estimate the association. Results. 38.1% patients had an overexpression of CD155, and the proportion of tumor cells with CD155 overexpression was 17%, 39%, 37%, and 62% among Luminal A, Luminal B, HER2-positive, and triple negative breast cancer cases, respectively (p<0.05). Patients with CD155 overexpression had the Ki-67 index significantly higher than that of patients with low expression (42% vs. 26%). Though the number of tumor-infiltrating lymphocytes was higher among patients with CD155 overexpression (144/HPF vs. 95/HPF), the number of PD-1+ lymphocytes was significantly higher (52/HPF vs. 25/HPF, p<0.05). Patients of CD155 overexpression had the disease-free and overall survival decreased by 13 months and 9 months, respectively (p<0.05). CD155 overexpression was associated with an increased relapse (HR=13.93, 95% CI 2.82, 68.91) and death risk for breast cancer patients (HR=5.47,1.42,20.99). Conclusions. Overexpression of CD155 was correlated with more proliferative cancer cells and a dysfunctional immune microenvironment. CD155 overexpression introduced a worse relapse-free and overall survival and might be a potential immunotherapy target for breast cancer.

scholarly journals Increased CD3+, CD8+, or FoxP3+ T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 808
Author(s):  
Ana Margarida Barbosa ◽  
Olga Martinho ◽  
Rosete Nogueira ◽  
Juliana Campos ◽  
Liliana Lobo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Indicators ◽  
Tumor Margins ◽  
Node Metastases ◽  
Infiltrating Lymphocytes

Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3+, CD8+, and FoxP3+ T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3+, CD8+, or FoxP3+ T lymphocytes were associated with TNM stages I-II (p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases (p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3+ T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3+, CD8+, or FoxP3+T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3+ T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.

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