Prognostic and predictive value of tumor-infiltrating lymphocytes for clinical therapeutic research in patients with non-small cell lung cancer

// Dong-Qiang Zeng 1, 2, * , Yun-Fang Yu 1, * , Qi-Yun Ou 3, 4, * , Xiao-Yin Li 5 , Ru-Zhi Zhong 6 , Chuan-Miao Xie 4 , Qiu-Gen Hu 1 1 Department of Radiology, Affiliated Shunde First People’s Hospital of Southern Medical University, Foshan, Guangdong, P. R. China 2 School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, P. R. China 3 Department of Ultrasound, Affiliated Shunde First People’s Hospital of Southern Medical University, Foshan, Guangdong, P. R. China 4 Imaging Diagnostic and Interventional Center, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 5 Department of Medical Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China 6 Guangdong Agricultural Reclamation Central Hospital, Affiliated Zhanjiang Cancer Hospital of Guangdong Medical University, Zhanjiang, Guangdong, P. R. China * These authors have contributed equally to this work and were co-first authors Correspondence to: Qiu-Gen Hu, e-mail: hqiugen@126.com Chuan-Miao Xie, e-mail: xchuanm@126.com Keywords: meta-analysis, molecular subtypes, non-small cell lung cancer, survival, tumor-infiltrating lymphocytes Received: November 09, 2015 Accepted: January 28, 2016 Published: February 09, 2016 ABSTRACT Background: Previous preclinical and clinical studies have shown that levels of tumor-infiltrating lymphocytes (TILs) significantly correlated with prognosis in non-small cell lung cancer (NSCLC), and survival after therapy; however, this finding remains controversial. We performed a meta-analysis, to evaluate, systematically, the clinical utilization of TIL subtypes in patients with NSCLC. Methods: The PubMed, ISI Web of Science, EMBASE, and Cochrane Library databases were searched to identify relevant studies. We pooled estimates of treatment effects, and hazards were summarized using random or fixed effects models to evaluate survival outcomes. Results: A total of 24 relevant studies involving 7,006 patients were eligible. The median percentage of lymph node positivity was 45.7% (95% confidence interval [CI], 37.1–56.4%). Pooled analysis shows that high levels of CD8 + TILs had a good prognostic effect on survival with a hazard ratio (HR) of 0.91 ( P = 0.013) for death and 0.74 ( P = 0.001) for recurrence, as did high levels of CD3 + and CD4 + TILs, with HRs of 0.77 ( P = 0.009) and 0.78 ( P = 0.005) for death, respectively. By contrast, high levels of FoxP3 + regulatory TILs had a worse prognostic effect for overall and recurrence-free survival, with HRs of 1.69 ( P = 0.042) and 1.79 ( P = 0.001), respectively. No individual study affected the results, and no publication bias was found. Conclusions: Our findings support the hypothesis that TILs could be a prognostic marker in NSCLC. High-quality randomized studies are needed to verify statistically the effect of TILs on prognosis in future research.