TY  - JOUR
A1  - Niesel, Katja Anne
A1  - Schulz, Michael
A1  - Anthes, Julian
A1  - Alekseeva, Tijna
A1  - Macas, Jadranka
A1  - Salamero-Boix, Anna
A1  - Möckl, Aylin
A1  - Oberwahrenbrock, Timm
A1  - Lolies, Marco
A1  - Stein, Stefan
A1  - Plate, Karl
A1  - Reiss, Yvonne
A1  - Rödel, Franz
A1  - Sevenich, Lisa
T1  - The immune suppressive microenvironment affects efficacy of radio-immunotherapy in brain metastasis
T2  - EMBO molecular medicine
N2  - 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.
KW  - brain cancer
KW  - checkpoint inhibitors
KW  - microglia
KW  - tumor microenvironment
KW  - tumor-associated macrophages
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/61548
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-615482
SN  - 1757-4684
VL  - 13
IS  - 5, art. e13412
SP  - 1
EP  - 19
PB  - Wiley-VCH
CY  - Weinheim
ER  -