Tom van den Ende1, Héctor G van den Boorn2, Nadine M Hoonhout2, Faridi S van Etten-Jamaludin3, Sybren L Meijer4, Sarah Derks5, Tanja D de Gruijl5, Maarten F Bijlsma6, Martijn G H van Oijen2, Hanneke W M van Laarhoven2. 1. Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address: t.vandenende@amsterdamumc.nl. 2. Amsterdam UMC, University of Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands. 3. Amsterdam UMC, University of Amsterdam, Research Support, Medical Library AMC, Meibergdreef 9, Amsterdam, the Netherlands. 4. Amsterdam UMC, University of Amsterdam, Department of Pathology, Cancer Center Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands. 5. Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Medical Oncology, Cancer Center Amsterdam, De Boelelaan 1117, Amsterdam, the Netherlands. 6. Amsterdam UMC, University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, Cancer Center Amsterdam, Oncode Institute, Meibergdreef 9, Amsterdam, the Netherlands.
Abstract
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.
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 cancerpatients (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.
Authors: Jons W van Hattum; Ben-Max de Ruiter; Jorg R Oddens; Maarten C C M Hulshof; Theo M de Reijke; Adriaan D Bins Journal: Cancers (Basel) Date: 2021-12-22 Impact factor: 6.639