OX40 and 4-1BB delineate distinct immune profiles in sarcoma.

Autor:	Melake MJ; Targeted Therapy Team, The Institute of Cancer Research, London, UK., Smith HG; Targeted Therapy Team, The Institute of Cancer Research, London, UK.; Digestive Disease Center, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Denmark., Mansfield D; Translational Immunotherapy Team, The Institute of Cancer Research, London, UK., Davies E; Targeted Therapy Team, The Institute of Cancer Research, London, UK.; The Royal Marsden Hospital, London, UK., Dillon MT; Targeted Therapy Team, The Institute of Cancer Research, London, UK.; The Royal Marsden Hospital, London, UK., Wilkins AC; The Royal Marsden Hospital, London, UK., Patin EC; Targeted Therapy Team, The Institute of Cancer Research, London, UK., Pedersen M; Translational Immunotherapy Team, The Institute of Cancer Research, London, UK., Buus R; The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK., Melcher AA; Translational Immunotherapy Team, The Institute of Cancer Research, London, UK.; The Royal Marsden Hospital, London, UK., Thway K; The Royal Marsden Hospital, London, UK., Miah AB; The Royal Marsden Hospital, London, UK., Zaidi SH; The Royal Marsden Hospital, London, UK., Hayes AJ; The Royal Marsden Hospital, London, UK., Fenton TR; University of Southampton, Somers Cancer Research Building MP824, Southampton General Hospital, Southampton, UK., Harrington KJ; Targeted Therapy Team, The Institute of Cancer Research, London, UK.; The Royal Marsden Hospital, London, UK., McLaughlin M; Targeted Therapy Team, The Institute of Cancer Research, London, UK.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2022 May 09; Vol. 11 (1), pp. 2066050. Date of Electronic Publication: 2022 May 09 (Print Publication: 2022).
DOI:	10.1080/2162402X.2022.2066050
Abstrakt:	Systemic relapse after radiotherapy and surgery is the major cause of disease-related mortality in sarcoma patients. Combining radiotherapy and immunotherapy is under investigation as a means to improve response rates. However, the immune contexture of sarcoma is understudied. Here, we use a retrospective cohort of sarcoma patients, treated with neoadjuvant radiotherapy, and TCGA data. We explore therapeutic targets of relevance to sarcoma, using genomics and multispectral immunohistochemistry to provide insights into the tumor immune microenvironment across sarcoma subtypes. Differential gene expression between radioresponsive myxoid liposarcoma (MLPS) and more radioresistant undifferentiated pleomorphic sarcoma (UPS) indicated UPS contained higher transcript levels of a number of immunotherapy targets (CD73/ NT5E , CD39/ ENTPD1 , CD25/ IL2RA , and 4-1BB/ TNFRSF9 ). We focused on 4-1BB/ TNFRSF9 and other costimulatory molecules. In TCGA data, 4-1BB correlated to an inflamed and exhausted phenotype. OX40/ TNFRSF4 and 4-1BB/ TNFRSF9 were highly expressed in sarcoma subtypes versus other cancers. Despite OX40 and 4-1BB being described as Treg markers, we identified that they delineate distinct tumor immune profiles. This was true for sarcoma and other cancers. While only a limited number of samples could be analyzed, spatial analysis of OX40 expression identified two diverse phenotypes of OX40+ Tregs, one associated with and one independent of tertiary lymphoid structures (TLSs). Patient stratification is of intense interest for immunotherapies. We provide data supporting the viewpoint that a cohort of sarcoma patients, appropriately selected, are promising candidates for immunotherapies. Spatial profiling of OX40+ Tregs, in relation to TLSs, could be an additional metric to improve future patient stratification. Competing Interests: No potential conflict of interest was reported by the author(s). (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)
Databáze:	MEDLINE
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