The immune suppressive microenvironment affects efficacy of radio-immunotherapy in brain metastasis

  • The tumor microenvironment in brain metastases is characterized by high myeloid cell content associated with immune suppressive and cancer-permissive functions. Moreover, brain metastases induce the recruitment of lymphocytes. Despite their presence, T-cell-directed therapies fail to elicit effective anti-tumor immune responses. Here, we seek to evaluate the applicability of radio- immunotherapy to modulate tumor immunity and overcome inhibitory effects that diminish anti-cancer activity. Radiotherapy- induced immune modulation resulted in an increase in cytotoxic T-cell numbers and prevented the induction of lymphocyte-mediated immune suppression. Radio-immunotherapy led to significantly improved tumor control with prolonged median survival in experi- mental breast-to-brain metastasis. However, long-term efficacy was not observed. Recurrent brain metastases showed accumula- tion of blood-borne PD-L1+ myeloid cells after radio-immunother- apy indicating the establishment of an immune suppressive environment to counteract re-activated T-cell responses. This finding was further supported by transcriptional analyses indicat- ing a crucial role for monocyte-derived macrophages in mediating immune suppression and regulating T-cell function. Therefore, selective targeting of immune suppressive functions of myeloid cells is expected to be critical for improved therapeutic efficacy of radio-immunotherapy in brain metastases.
Author:Katja Niesel, Michael Schulz, Julian Anthes, Tijna Alekseeva, Jadranka Macas, Anna Salamero-Boix, Aylin Möckl, Timm Oberwahrenbrock, Marco Lolies, Stefan Stein, Karl Plate, Yvonne Reiss, Franz RödelORCiDGND, Lisa Sevenich
Parent Title (English):EMBO molecular medicine
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/03/23
Date of first Publication:2021/03/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/07/21
Tag:brain cancer; checkpoint inhibitors; microglia; tumor microenvironment; tumor-associated macrophages
Issue:5, art. e13412
Page Number:19
First Page:1
Last Page:19
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0