Iwahori et al. analyzed tumors, normal lung tissue, and peripheral blood from patients with early-stage NSCLC for T cell markers, cytokine production, and cytotoxic capability (using a bispecific T-cell engager and a surrogate tumor cell line for the latter). Cytotoxicity of CD8+ T cells (mostly CD45RA+ effector memory) in peripheral blood correlated with cytotoxicity of tumor-infiltrating T cells. There was some overlap in TCR clonotypes between the three sample types. Cytotoxic capacity of peripheral blood T cells correlated with nivolumab efficacy in a small data set, suggesting the possibility of blood-based diagnostics as a predictive biomarker.
Cancer immunotherapy, including immune checkpoint inhibitors, exerts beneficial effects in cancer patients. However, immune checkpoint inhibitors are only advantageous for a limited population of cancer patients. Therefore, companion diagnostics are needed in order to identify patients for whom these therapies are effective. In the present study, we evaluated detailed immunological aspects in clinical specimens from non-small cell lung cancer (NSCLC) patients. We analyzed the immune profiles, T cell cytotoxicity, and TCR repertoire of peripheral blood, normal lung tissue, and tumor tissue from NSCLC patients. By using bispecific T-cell engager technology to assess the cytotoxicity of T cells, we found that the cytotoxicity of tumor-infiltrated T cells closely correlated with that of peripheral T cells. This correlation was supported by the immune profiles, cytokine production, and results of the TCR repertoire analysis from these specimens. We also found that the cytotoxicity of peripheral T cells has potential as a predictor of the effects of nivolumab in the tumor microenvironment. These results imply further applications to blood-based immune monitoring systems and predictive biomarkers for cancer immunotherapy.