Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients.

Simple Summary: The content as well as the status of immune cells before immunotherapy administration are indispensable for response. TAA-specific T cells have been associated with poor responses to chemotherapy. However, their role as predictive biomarkers for immunotherapy administration as well as their interplay with other immune system cells is not well understood. Our findings reveal that combined analysis of pre-existing immunity T cells of different immune parameters in treatment-naïve NSCLC patients leads to better prediction tools for immunotherapy response. T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI⁺) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3⁺IFNγ⁺ cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI⁺ T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI⁺ patients compared to PreI^– patients (not reached vs. 321 days, respectively; p = 0.014). PreI⁺ patients had significantly higher numbers of possible exhausted CD3⁺CD8⁺PD-1⁺ cells and lower percentages of immunosuppressive Tregs compared to PreI⁻ patients. Additionally, patients with PreI⁺ and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens. [ABSTRACT FROM AUTHOR]