Circulating cell populations as response predictors and targets to improve immunotherapy in metastatic lung cancer

Here, we profiled baseline systemic immunity in patients with stage IV NSCLC treated with anti-PD-1 plus chemotherapy to identify immune mechanisms and circulating biomarkers associated with response. We prospectively enrolled 33 treatment-naive patients, including 22 responders and 11 non-responders at week 9, and 17 responders and 16 non-responders at 6 months.

Responders showed increased frequencies of circulating T cells expressing CD69, TCF-1, and CXCR3. In contrast, non-responders exhibited higher frequencies of CTLA-4-, CD161-, and IL-10-expressing CD4+ and CD8+ T cells. These systemic immune profiles were mirrored in the tumor microenvironment in an independent cohort.