Immune niches in brain metastases contain TCF1+ stem-like T cells, are associated with disease control and are modulated by preoperative SRS.

• Type of Material: Article
• Authors: Hal Scherz, Emory University; Caroline Jansen, Emory University; Roshan Prabhu, Levine Cancer Institute, Atrium Health, Charlotte; Meghana Pagadala, University of California San Diego; Prasanthi Chappa, Emory University; Subir Goyal, Emory University; Chengjing Zhou, Emory University; Stewart Neill, Emory University; Nataliya Prokhnevska, Emory University; Maria Cardenas, Emory University; Kimberly Hoang, Emory University; Jim Zhong, Emory University; Mylin Torres, Emory University; Suzanna Logan, Nationwide Children’s Hospital, Columbus; Jeffrey Olson, Emory University; Edjah Nduom, Emory University; Luke Del Balzo, Emory University; Kirtesh Patel, Kaiser Permanente, Atlanta; Stuart Burri, Levine Cancer Institute, Atrium Health; Anthony Asher, Atrium Health, Charlotte; Scott Wilkinson, National Cancer Institute, Bethesda; Ross Lake, National Cancer Institute, Bethesda; Krisitin Higgins, Emory University; Pretesh Patel, Emory University; Vishal Dhere, Emory University; Adam Sowalsky, National Cancer Institute, Bethesda; Mohammad Khan, Emory University; Haydn Kissick, Emory University; Zachary Buchwald, Emory University
• Language: English
• Date: 2023-03-23
• Publisher: Research Square
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: © Research Square 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.21203/rs.3.rs-2722744/v1
• Title of Journal or Parent Work: Res Sq
• Grant/Funding Information: Zachary Buchwald is supported by a National Cancer Institute grant (1-K12-CA-237806-01), American Cancer Society Clinical Scientist Development Grant, Melanoma Research Alliance Young Investigator Award.; Caroline Jansen is supported by a National Cancer Institute grant (1-F30-CA-243250).
• Keywords: Immune niches

Abstract

The CD8 + T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1 + TCF1 + stem-like CD8 + T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS’s impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8 + T cells at 3 days. However, CD8 + T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1 + stem-like population.