Compartmental analysis of T cell clonal dynamics as a function of pathologic response to neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Purpose: Neoadjuvant PD-1 blockade is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet immunological mechanisms contributing to tumor regression and biomarkers of response are unknown. Using paired tumor/blood samples from a phase 2 clinical trial (NCT02259621), we explored whether the peripheral T cell clonotypic dynamics can serve as a biomarker for response to neoadjuvant PD-1 blockade. Experimental Design: T cell receptor (TCR) sequencing was performed on serial peripheral blood, tumor and normal lung samples from resectable NSCLC patients treated with neoadjuvant PD-1 blockade. We explored the temporal dynamics of the T cell repertoire in the peripheral and tumoral compartments in response to neoadjuvant PD-1 blockade by using the TCR as a molecular barcode. Results: Higher intratumoral TCR clonality was associated with reduced percent residual tumor at the time of surgery, and the TCR repertoire of tumors with major pathologic response (MPR;