Systemic immune parameters after prior radiation therapy in patients receiving immune checkpoint inhibitors.

Abstract

INTRODUCTION:

Preclinical studies have demonstrated the ability of radiation therapy (RT) to augment immune response and tumor control by immune checkpoint inhibitors (ICI). However, numerous clinical trials combining RT and ICI have yielded relatively disappointing results. To improve understanding of optimal use of these therapies, we assessed systemic immune effects of prior RT in patients receiving ICI.

METHODS AND MATERIALS:

Pre- and post-ICI blood samples were collected from patients enrolled in a prospective immunotherapy biospecimen protocol. Mutiplex panels of 40 cytokines and 120 autoantibodies (Ab) were analyzed. We identified differences in these parameters according to receipt, timing, and type of prior RT. We calculated P values using the Pearson product-moment correlation coefficient and false discovery rate (FDR) using the Benjamini-Hochberg Procedure.

RESULTS:

Among 277 total patients, 69 (25%) received RT in the 6 months prior to ICI initiation. Among RT-treated patients, 23 (33%) received stereotactic RT, and 33 (48%) received curative intent RT. There was no significant difference in demographics or type of immunotherapy between patients according to prior RT exposure. Baseline complement C8 Ab and MIP-1d/CCL15 were significantly higher among patients with prior RT. For MIP-1d/CCL15, only prior stereotactic RT was associated with significant differences.

CONCLUSIONS:

Prior RT is associated with few changes in systemic immune parameters in patients receiving ICI. The underlying mechanisms and optimal approach to harnessing the potential synergy of RT and ICI require further prospective clinical investigation.

• Authors: Vatsala Mundra, Yuqiu Yang, Mitchell S von Itzstein, Farjana Fattah, Amrit S Gonugunta, Raquibul Hannan, Laurentiu M Pop, Yuanyuan Zhang, Yiqing Wang, Thomas Sheffield, Yang Xie, Jonathan E Dowell, Jade Homsi, Sawsan Rashdan, Jason Park, Quan-Zhen Li, Edward K Wakeland, David E Gerber
• Journal: Translational oncology (Transl Oncol) Vol. 34 Pg. 101689 (Aug 2023) ISSN: 1936-5233 [Print] United States
• PMID: 37285748 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.