Evaluation of Tumor Immune Microenvironment Changes in Response to Different Radiotherapy Regimens in a CT26 Tumor Model

Masoumeh Alimohammadi; Haniyeh Ghaffari Nazari; Reza Alimohammadi; Mohsen Bakhshandeh; Seyed Amir Jalali; Nima Rezaei

doi:10.18502/igj.v8i1.17995

Masoumeh Alimohammadi Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Haniyeh Ghaffari Nazari Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Reza Alimohammadi Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mohsen Bakhshandeh Department of Radiology Technology, Allied Medical Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Seyed Amir Jalali Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Nima Rezaei Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/igj.v8i1.17995

Keywords: Radiotherapy; Immune Response; Immune Checkpoint Inhibitor; CT26 Colon Cancer

Abstract

Background: Radiotherapy (RT) is vital in cancer treatment, inducing tumor cell death and anti-tumor immunity. However, it can also enhance immunosuppressive factors like CD47 and PD-L1. While RT- immunotherapy combinations show promise, optimal strategies remain unclear. This study examines the impact of different RT regimens on the tumor immune microenvironment (TME) to guide more effective treatment approaches.

Methods: We treated CT26 tumor-bearing mice with three distinct RT regimens under the same biological equivalent dose (BED).

Result: We observed that the frequency of both tumor-infiltrating CD4+ and CD8+ cells were increased after ablative and hypo RT, although single high dose exposure in an ablative scheme led to a greater extent of CD8+ cells infiltration and increased the expression of IFNγ in those cells. While conventional RT enhanced the recruitment of myeloid-derived suppressor cells (MDSCs) into tumors, the Ablative and hypo schemes induced regulatory T cells (Tregs) enrichment. The two hypofractionated regimens enhanced the expression of CD47 as well as the PD-1/PD-L1 axis, although PD-1 and its ligand (PD-L1) expression were temporarily induced by conventional RT on tumor-infiltrating lymphocytes and tumor cells, respectively.

Conclusion:The results suggest targeting the recruitment of MDSC and Treg are, respectively, crucial for therapeutic efficacy of conventional and hypofractionated RT regimens. Furthermore, anti-PD-1/PD-L1 and anti-CD47 treatments are necessary to improve the anti-tumor response from the hypofractionated schemes.