Tumor Infiltrating Lymphocytes as a Predictive Biomarker for Response to CTLA-4 and PDL-1 Therapies

Abstract

Recently approved immunotherapies capitalize on antitumor mechanisms of the patient’s immune system by inhibiting CTLA-4 and PD-1 pathways. Studies have shown better overall survival with increased tumor infiltrating lymphocyte (TIL) across multiple cancer. Recent trials with anti-PDL-1 has shown better response with high PDL-1 expression. However, studies have not evaluated whether TIL level would correlate with anti-PDL-1 or anti-CTLA-4 responses. The aim of this study is to determine if the level of TIL in metastatic melanoma and lung cancer correlates with patient response to modern immunotherapies. We identified 10 patients with melanoma or lung cancer treated with an immune checkpoint inhibitor. The biopsy samples were stratified according to level of TIL. The TIL categories ranged from 0 to 3, with 0 indicating no TIL detected and 3 indicating 67-100% TIL infiltration. Survival analysis was achieved with Kaplan-Meier curve, and tumor size change was evaluated with linear mixed model analysis. Overall survival was significantly longer in patients who had TIL (TIL0-0.3 yr; TIL1-2-2.4 yr; TIL3-1.6 yr, p=0.024). Tumor size also dramatically decreased at first follow up based on TIL level (TIL 1-2: 371% greater decrease than TIL 0, p < 0.01; TIL 3: 406%; p<0.01). Decrease in tumor size for TIL0 was 0.12cm2 at first follow-up. Baseline tumor size for TIL0 was 41.9cm2; TIL1-2 0.4 cm2; TIL3 1.4cm2. Our study shows that TIL level may serve as a biomarker to predict tumor response to immunotherapy, without specific histochemical staining. This study is limited by the low number; a larger review is currently taking place.