Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Autor:	Orozco JIJ; Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States., Valdez BJ; Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States., Matsuba C; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States., Simanonok MP; Center for Cardiovascular Analytics, Research and Data Science, Providence Research Network, Portland, OR, United States., Ensenyat-Mendez M; Cancer Epigenetics Laboratory at the Cancer Cell Biology Group, Institut d'Investigació Sanitària Illes Balears (IdISBa), Palma, Spain., Ramiscal JAB; Department of Surgical Oncology, Arrowhead Regional Medical Center & California University of Science and Medicine, Colton, CA, United States., Salomon MP; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States., Takasumi Y; Department of Pathology, Providence Saint John's Health Center, Santa Monica, CA, United States., Grumley JG; Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Apr 24; Vol. 15, pp. 1373497. Date of Electronic Publication: 2024 Apr 24 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1373497
Abstrakt:	Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p =0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation ( p <0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death ( p <0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Orozco, Valdez, Matsuba, Simanonok, Ensenyat-Mendez, Ramiscal, Salomon, Takasumi and Grumley.)
Databáze:	MEDLINE
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