Expressions of CD8+TILs, PD-L1 and Foxp3+TILs in stage I NSCLC guiding adjuvant chemotherapy decisions

Abstract

PurposeCurrently, adjuvant chemotherapy is recommended for patients with high risk stage I non-small cell lung cancer (NSCLC). However, identifying high risk patients remains a challenge. This study aims to identify the patient cohorts more likely to benefit from adjuvant chemotherapy based on the tumor micro-immune environment.ResultsCD8+TILs significantly associated with disease-free survival (DFS) and overall survial (OS) (p=0.002; 0.040). Patients with high risk factors may also predict shorter DFS (P=0.056). When compared together, patients with high-CD8+TILs showed better DFS than patients with low-CD8+TILs, no matter their risk factors status. There's no correlation between PD-L1 expressions and survival. PD-L1 was highly expressed in men, squamous and well differentiated carcinoma. In addition, Foxp3+TILs alone didn't show any prognostic effects, but low-Foxp3/high-CD8+TILs were associated with prolonged DFS (p=0.031).MethodsA total of 126 patients with surgically resected stage I NSCLC were included to perform immunohistochemistry of CD8+ tumor infiltrating lymphocytes (TILs), programmed death ligand-1(PD-L1) and forkhead box P3 (Foxp3)+TILs.ConclusionCD8+TILs are effective prognostic predictors. Patients with surgically resected stage I NSCLC showing low CD8+TILs could be considered for adjuvant chemotherapy, even if they have no high risk features.

Prognostic impact of CD8 and programmed death-ligand 1 expression in patients with resectable non-small cell lung cancer

“…A study that included patients with surgically resected stage I NSCLC showed that CD8+TILs, but not PD-L1, was associated with increased disease-free survival (DFS) and OS. 13 In another study showing similar findings, a positive impact of CD8+ expression on survival of resected NSCLC patients was shown only in those with low PD-1-to-CD8 ratio. 21 A French study for patients with surgically treated basaloid squamous cell lung carcinoma (stage I-II, 68%) reported that patients with high PD-L1 expression together with increased PD-1+ and CD8+TILs were associated with an 87% reduction of death risk compared to those with low expression of all three markers.…”

“…However, inconsistent findings from positive to negative or insignificant results were reported for the prognostic value of these biomarkers. 13,[21][22][23][24] In this study, we suggest additional findings for clinical impact of expression of CD8 and PD-L1 as prognostic biomarkers in NSCLC patients treated with surgical resection.…”

“…6,7 However, there are debates about whether PD-L1 has a prognostic role in locoregional disease. [13][14][15][16] Various cut-off values and methodologies to assess the expression of PD-L1 may partly explain this inconsistency. Furthermore, given that PD-L1 is inducible and may reflect www.nature.com/bjc homoeostatic responses to immune activation, 17 immune cell infiltration should be considered simultaneously to assess the prognostic role of PD-L1 expression.…”

Tumor‐infiltrating CD8+ T‐cell density is an independent prognostic marker for oral squamous cell carcinoma

“…Meta‐analyses revealed that CD8 + T cells have a positive effect on OS, with a HR of 0.71 (95% CI 0.62‐0.82), and are effective prognostic predictors for OS and DSS in breast cancer . CD8 + T cells were also predictors for OS and disease‐free survival (DFS) in stage I non‐small cell lung cancer …”

“…28 CD8 + T cells were also predictors for OS and disease-free survival (DFS) in stage I non-small cell lung cancer. 29 A recent meta-analysis on tumor-infiltrating immune cells suggested that the amount and density of tumor-infiltrating CD8 + T cell also affected survival in HNSCC patients, 30 whereas there is controversy as to whether higher levels of tumor-infiltrating CD8 + T cells improve survival in patients with OSCC. Several studies indicated that tumor-infiltrating immune cells did not provide any survival benefit in patients with OSCC.…”