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Low PD-1 Expression in Cytotoxic CD8 + Tumor-Infiltrating Lymphocytes Confers an Immune-Privileged Tissue Microenvironment in NSCLC with a Prognostic and Predictive Value.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2018 Jan 15; Vol. 24 (2), pp. 407-419. Date of Electronic Publication: 2017 Oct 26. - Publication Year :
- 2018
-
Abstract
- Purpose: The success of immune checkpoint inhibitors strengthens the notion that tumor growth and regression are immune regulated. To determine whether distinct tissue immune microenvironments differentially affect clinical outcome in non-small cell lung cancer (NSCLC), an extended analysis of PD-L1 and tumor-infiltrating lymphocytes (TIL) was performed. Experimental Design: Samples from resected adenocarcinoma (ADC 42), squamous cell carcinoma (SCC 58), and 26 advanced diseases (13 ADC and 13 SCC) treated with nivolumab were analyzed. PD-L1 expression and the incidence of CD3, CD8, CD4, PD-1, CD57, FOXP3, CD25, and Granzyme B TILs were immunohistochemically assessed. Results: PD-L1 levels inversely correlated with N involvement, although they did not show a statistically significant prognostic value in resected patients. The incidence and phenotype of TILs differed in SCC versus ADC, in which EGFR and KRAS mutations conditioned a different frequency and tissue localization of lymphocytes. NSCLC resected patients with high CD8 <superscript>pos</superscript> lymphocytes lacking PD-1 inhibitory receptor had a longer overall survival (OS: HR = 2.268; 95% CI, 1.056-4.871, P = 0.03). PD-1-to-CD8 ratio resulted in a prognostic factor both on univariate (HR = 1.952; 95% CI, 1.34-3.12, P = 0.001) and multivariate (HR = 1.943; 95% CI, 1.38-2.86, P = 0.009) analysis. Moreover, low PD-1 incidence among CD8 <superscript>pos</superscript> cells was a distinctive feature of nivolumab-treated patients, showing clinical benefit with a prolonged progression-free survival (PFS: HR = 4.51; 95% CI, 1.45-13.94, P = 0.004). Conclusions: In the presence of intrinsic variability in PD-L1 expression, the reservoir of PD-1-negative effector T lymphocytes provides an immune-privileged microenvironment with a positive impact on survival of patients with resected disease and response to immunotherapy in advanced NSCLC. Clin Cancer Res; 24(2); 407-19. ©2017 AACR .<br /> (©2017 American Association for Cancer Research.)
- Subjects :
- Aged
Biomarkers, Tumor
CD8-Positive T-Lymphocytes immunology
Carcinoma, Non-Small-Cell Lung mortality
Carcinoma, Non-Small-Cell Lung pathology
Female
Humans
Lung Neoplasms mortality
Lung Neoplasms pathology
Lymphocytes, Tumor-Infiltrating immunology
Male
Middle Aged
Mutation
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Proportional Hazards Models
CD8-Positive T-Lymphocytes metabolism
Carcinoma, Non-Small-Cell Lung etiology
Carcinoma, Non-Small-Cell Lung metabolism
Lung Neoplasms etiology
Lung Neoplasms metabolism
Lymphocytes, Tumor-Infiltrating metabolism
Programmed Cell Death 1 Receptor genetics
Tumor Microenvironment
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 24
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 29074606
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-17-2156