Data from Peripheral Th17 Immune Signature Associates with Excellent Response to Anti–PD-1/Anti–PD-L1 Therapy across Solid Tumors
Year: 2026
Type: other
Abstract: Immune checkpoint inhibitors (ICI) have transformed cancer care, at times generating durable partial response (PR) or even complete response (CR) in advanced cancers. However, only a minority of patients experience these “excellent” responses. Thus, there is a need for novel biomarkers that can identify those with robust clinical benefit. To address this, we prospectively collected blood samples from 124 patients with advanced and/or metastatic pan-solid tumors treated as standard of care with anti–PD-1 or anti–PD-L1 alone or in combination with other agents. In this cohort, 30 of 124 (24.2%) patients were classified as excellent responders (ER), defined as experiencing a CR or a durable PR with progression-free survival (PFS) ≥1 year. Peripheral immune cells were analyzed by cytometry by time of flight, and cytokines were analyzed using a multiplex immunoassay. At baseline and early-on-treatment, ERs had elevated concentrations of Th17-associated cytokines, IL17F, IL21, and IL23 and decreased IL8 compared with non-ERs (P < 0.05). Elevated on-treatment IL6 was also associated with non-ERs (P < 0.05). High baseline IL17F and IL23 were associated with superior PFS, and high baseline IL8 was associated with inferior overall survival (P < 0.05). Non-ERs demonstrated decreased proportions of Th17 cells from baseline to early-on-treatment. Regression analysis of functional markers in non-ERs showed a proliferation of exhaustion-like Th17 cells (Ki67+TIGIT+) from baseline to early-on-treatment (P < 0.01) that was not present in ERs. This study identifies the Th17 pathway as a potential correlate of excellent ICI response and represents a comprehensive exploration of peripheral immune signatures associated with durable ICI benefit.
Authors: Howard L. Li, Soren Charmsaz, Chester Kao, Carlotta Pazzi, Madelena Brancati, James M. Leatherman, Luke X. Zhao, Waqar Arif, Royce P. Lee, Jeric Hernandez, Nicole E. Gross, Caroline Ellis, Christopher Thoburn, Yasser Ged, Jeannie Hoffman-Censits, Evan J. Lipson, Marina Baretti, G. Scott Chandler, Rajat Mohindra, Laura Tang, Sanjay Bansal, Aditi Guha, Elizabeth M. Jaffee, Daniel J. Zabransky, Won J. Ho, Mark Yarchoan, Mari Nakazawa
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7204997588
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