Autoantibody spark response predicts prognosis in patients receiving chemoradiation followed by durvalumab therapy

Background Chemoradiotherapy (CRT), followed by adjuvant durvalumab therapy, also known as the PACIFIC regimen, is the standard treatment for patients with advanced non-small cell lung cancer. However, there is a lack of reliable predictive biomarkers for immune monitoring of residual microtumors after chemoradiotherapy. Methods Serum samples were collected at three time points: on the day CRT commenced, on the final day of CRT, and two weeks after the first dose of durvalumab. We investigated autoantibody responses using a 130-multiplexed autoantigen panel comprising cancer-testis antigens, tumor-associated antigens, tumor markers, and autoimmunity antigens. Results We observed an immediate and strong autoantibody response after initiating adjuvant durvalumab therapy in patients with favorable prognoses. Tumor PD-L1 expression before chemoradiotherapy served as an independent prognostic biomarker, and combining PD-L1 expression with autoantibody spark response further enhanced the accuracy of prognostic predictions. Conclusions Monitoring autoantibody panels using small aliquots of peripheral blood provides insights into antitumor immune reactions even in clinically non-detectable residual microtumors, and enhances the precision of prognostic predictions.