Response to Chemoimmunotherapy Is Associated With Expansion of Systemic Antitumor CD4⁺ Th1 Response in Metastatic Non–Small Cell Lung Cancer

Abstract

Limited data have reported the evolution of antitumor immune responses under chemoimmunotherapy (chemo-IO) in patients with metastatic non–small cell lung cancer. In this concise study, we performed dynamic monitoring of antitumor CD4⁺ T helper 1 (Th1) response in peripheral blood from 12 patients receiving a first-line chemo-IO. Tumor-reactive CD4⁺ Th1 cells were assessed within blood lymphocytes using interferon-gamma enzyme-linked immunospot assay to detect telomerase (TERT)-specific T cells at baseline, 3 and 12 months after treatment. An induction of circulating anti-TERT CD4⁺ Th1 response were found in 6 of 12 patients at 3 months after chemo-IO. In contrast, 3 patients had a substantial decrease in their preexisting response and 3 remained nonimmune responders. Among patients with chemo-IO-induced immune response, half achieved an objective clinical response and had long-lasting circulating anti-TERT CD4⁺ Th1 cells detected for at least 1 year. In contrast, no objective response was documented in nonimmune responders and a link between the loss of anti-TERT CD4⁺ Th1 responses were observed in patients with progressive disease. This preliminary work supports a relationship between the efficacy of combinatorial chemo-IO and circulating anti-TERT CD4⁺ Th1 responses and highlights the interest to implement blood-based monitoring of tumor-reactive CD4⁺ T cells that could be additional help for patient management.