The current understanding of the immune landscape relative to radiotherapy across tumor types

Sep 24, 2026

Radiotherapy is a standard cancer therapy that directly affects tumor cells and the surrounding milieu, simultaneously priming and potentially restricting antitumor immunity. This review explains how a heterogeneous immune tumor microenvironment and systemic immunity—collectively termed the immune landscape—shape response dynamics and complicate prediction. Common post-irradiation patterns include increased infiltrating T lymphocytes and PD-L1 upregulation, while lymphopenia and therapy-induced expansion of immunosuppressive populations such as M2 macrophages and MDSCs can hinder survival and efficacy. The article further emphasizes how treatment parameters themselves can be leveraged.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

AccessFree to download

Introduction

Immune landscape and tumor microenvironment

Pan-cancer immune classifications

TYPE Review PUBLISHED 16 March 2023 DOI 10.3389/fimmu.2023.1148692 OPEN ACCESS EDITED BY Shaoli Song, Fudan University, China REVIEWED BY Ana Vuletic´, Institute of Oncology and Radiology of Serbia, Serbia Ende Zhao, New York University, United States *CORRESPONDENCE Mohammad Krayem [mohammad.krayem@hubruxelles.be](mohammad.krayem@hubruxelles.be) SPECIALTY SECTION This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology RECEIVED 20 January 2023 ACCEPTED 03 March 2023 PUBLISHED 16 March 2023 CITATION Iliadi C, Verset L, Bouchart C, Martinive P, Van Gestel D and Krayem M (2023) The current understanding of the immune landscape relative to radiotherapy across tumor types. Front. Immunol. 14:1148692 . doi: 10.3389/fimmu.2023.1148692 COPYRIGHT © 2023 Iliadi, Verset, Bouchart, Martinive, Van Gestel and Krayem. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The current understanding of the immune landscape relative to radiotherapy across tumor types Chrysanthi Iliadi 1,2, Laurine Verset 3, Christelle Bouchart 1, Philippe Martinive 1, Dirk Van Gestel1 and Mohammad Krayem 1,2* 1 Department of Radiation Oncology, Institut Jules Bordet, Universite´ Libre de Bruxelles (ULB), Hˆopital Universitaire de Bruxelles (H. U. B), Brussels, Belgium, 2 Laboratory of Clinical and Experimental Oncology (LOCE), Institut Jules Bordet, Universite´ Libre de Bruxelles (ULB), Hˆopital Universitaire de Bruxelles (H. U. B), Brussels, Belgium, 3 Department of Pathology, Institut Jules Bordet, Universite´ Librede Bruxelles (ULB), Hˆopital Universitaire de Bruxelles (H. U. B), Brussels, Belgium Radiotherapy is part of the standard of care treatment for a great majority of cancer patients. As a result of radiation, both tumor cells and the environment around them are affected directly by radiation, which mainly primes but also might limit the immune response. Multiple immune factors play a role in cancer progression and response to radiotherapy, including the immune tumor microenvironment and systemic immunity referred to as the immune landscape. A heterogeneous tumor microenvironment and the varying patient characteristics complicate the dynamic relationship between radiotherapy and this immune landscape. In this review, we will present the current overview of the immunological landscape in relation to radiotherapy in order to provide insight and encourage research to further improve cancer treatment. An investigation into the impact of radiation therapy on the immune landscape showed in several cancers a common pattern of immunological responses after radiation . Radiation leads to an upsurge in inﬁltrating T lymphocytes and the expression of programmed death ligand 1 (PD-L1) which can hint at a beneﬁt for the patient when combined with immunotherapy. In spite of this, lymphopenia in the tumor microenvironment of ‘cold ’ tumors or caused by radiation is considered to be an important obstacle to the patient’s survival. In several cancers, a rise in the immunosuppressive populations is seen after radiation, mainly pro-tumoral M2 macrophages and myeloid-derived suppressor cells (MDSCs) . As a ﬁnal point, we will highlight how the radiation parameters themselves can inﬂuence the immune system and, therefore, be exploited to the advantage of the patient. KEYWORDS radiotherapy, cancer, systemic immune response, immune tumor microenvironment, immune landscape, biomarker, immune cells Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Introduct

FAQs

What does the review describe as the immune landscape in relation to radiotherapy?

It defines the immune landscape as a heterogeneous network of immune cells and immune components, including factors such as chemoattractants and tumor mutational burden, which help determine how tumors respond to treatment.

What immune changes after radiation are highlighted as potentially beneficial?

The review notes an upsurge in infiltrating T lymphocytes and increased PD-L1 expression, suggesting possible patient benefit when combined with immunotherapy.

What obstacles to survival does the review associate with radiotherapy in “cold” tumors?

It emphasizes lymphopenia within the tumor microenvironment of cold tumors or caused by radiation as an important obstacle to patient survival.

Sep 24, 2026

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