Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types

Tom van den Ende*, Héctor G. van den Boorn, Nadine M. Hoonhout, Faridi S. van Etten-Jamaludin, Sybren L. Meijer, Sarah Derks, Tanja D. de Gruijl, Maarten F. Bijlsma, Martijn G.H. van Oijen, Hanneke W.M. van Laarhoven

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review


Background: Chemotherapy (CT), radiotherapy (RT), and chemoradiotherapy (CRT) are able to alter the composition of the tumor immune microenvironment (TIME). Understanding the effect of these modalities on the TIME could aid in the development of improved treatment strategies. Our aim was to systematically review studies investigating the influence of CT, RT or CRT on different TIME markers. Methods: The EMBASE (Ovid) and PubMed databases were searched until January 2019 for prospective or retrospective studies investigating the dynamics of the local TIME in cancer patients (pts) treated with CT, RT or CRT, with or without targeted agents. Studies could either compare baseline and follow-up specimens - before and after treatment - or a treated versus an untreated cohort. Studies were included if they used immunohistochemistry and/or flow cytometry to assess the TIME. Results: In total we included 110 studies (n = 8850 pts), of which n = 89 (n = 6295 pts) compared pre-treatment to post-treatment specimens and n = 25 (n = 2555 pts) a treated versus an untreated cohort (4 studies conducted both comparisons). For several tumor types (among others; breast, cervical, esophageal, ovarian, rectal, lung mesothelioma and pancreatic cancer) remodeling of the TIME was observed, leading to a potentially more immunologically active microenvironment, including one or more of the following: an increase in CD3 or CD8 lymphocytes, a decrease in FOXP3 Tregs and increased PD-L1 expression. Both CT and CRT were able to immunologically alter the TIME. Conclusion: The TIME of several tumor types is significantly altered after conventional therapy creating opportunities for concurrent or sequential immunotherapy.

Original languageEnglish
Article number188386
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Issue number1
Publication statusPublished - Aug 2020

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