The association between CD8+ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy: A systematic review and meta-analysis

Abstract

Background: The responses of cancer patients to immune checkpoint inhibitors (ICIs) vary in success. CD8+ tumor infiltrating lymphocytes (TILs) play a key role in killing tumor cells. This study aims to evaluate the prognostic role of CD8+ TILs in cancer patients treated with ICIs. Methods: We systematically searched all publications from PubMed, EMBASE, and Cochrane Library until 12 Jul 2021 without any restriction of language or article types. Studies assessing high versus low CD8+ TILs in predicting efficacy and survival of various cancer patients were included. The outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). The study protocol is prospectively registered on PROSPERO (registration number CRD42021233654). Findings: Findings: A total of 33 studies consisting of 2559 cancer patients were included. The result showed that high CD8+ TILs were significantly associated with better OS (HR, 0.52; 95% confidence interval: 0.410.67; p < 0.001), PFS (HR, 0.52; 95% confidence interval: 0.400.67; p < 0.001) and ORR (OR, 4.08; 95% confidence interval: 2.736.10; p < 0.001) in patients treated with ICIs. Subgroup analyses suggested that patients with high CD8+ TILs had a better clinical benefit, regardless of different treatments (ICI mono therapy, or combination therapy), cancer types (NSCLC, melanoma and others), and CD8+ T cells locations (intratumor, stroma, and invasive margin). The higher baseline circulating CD8+ T cells from peripheral blood did not contribute to the improved OS (HR, 0.93; 95% confidence interval: 0.671.29; p = 0.67) and PFS (HR, 0.89; 95% confidence interval: 0.601.32; p = 0.56) compared with the low baseline. Interpretation: Interpretation: Our results suggested that high intra-tumoral, stromal, or invasive marginal, but not circulating CD8+ T cells, can predict treatment outcomes in patients with ICIs therapy across different cancers, in either single-agent ICIs or combination with other therapies.