An Immunologic Niche Of Antigen Presenting Cells And Stem-Like Cd8+T-Cells Is Present In Non-Small Cell Lung Cancer Brain Metastases.

Abstract Background: Non-small cell lung cancer (NSCLC) patients with brain metastases have a very poor prognosis. The first line treatments for NSCLC brain metastases are typically surgery and pre- or post-operative stereotactic radiosurgery (SRS) or SRS alone. However, subsequent intra-cranial failure and death is common. Importantly, we have previously shown that a unique immune niche in genitourinary malignancies correlates with the risk for disease recurrence. Accordingly, here we investigated whether this immune niche was present in brain metastases, whether it correlated with patient outcomes, and whether it was modulated by SRS. Methods: Formalin fixed paraffin embedded brain metastases were stained by immunofluorescence for CD8, PD-1, TCF-1, MHC-II and DAPI. Following successful image acquisition using fluorescent whole slide scanning, we used a custom quantitative analysis pipeline to measure the cellularity, relative cellular locations, local cellular density, and marker staining intensity. Results: We identified immune niches consisting of both stem-like TCF-1+ CD8+ T-cells and antigen presenting cells (MHC-II+) in brain metastases. TCF-1+ CD8+ T-cells were found at in areas of higher MHC-II+ cell density than the TCF-1 CD8+negative T-cells. The amount of tumor issue occupied by immune niches correlated with TCF1+ CD8+ T-cell infiltration, as well as with total CD8+ T-cell and MHC-II+ cell infiltration. Importantly, we found that higher MHC-II+ cell density correlated with longer overall survival in this cohort of patients. Additionally, we found this immune niche is preserved following pre-operative SRS. Conclusions: Our study is the first to demonstrate stem-like CD8+ T-cells in brain metastases and that these cells form an immune niche similar to those described extra-cranial tumor sites. Additionally, we report that the immune niche is preserved following SRS, which is highly clinically relevant to the use of combinatorial strategies between SRS and checkpoint blockade. Citation Format: Caroline S. Jansen, Luke del Balzo, Roshan Prabhu, Suzanna Logan, Prasanthi Chappa, Kirtesh Patel, Scott Wilkinson, Ross Lake, Hui-Kuo G. Shu, Jim Zhong, Vishal Dhere, Jeffrey Olson, Adam G. Sowalsky, Mohammad K. Khan, Haydn T. Kissick, Zachary S. Buchwald. An immunologic niche of antigen presenting cells and stem-like CD8+ T-cells is present in non-small cell lung cancer brain metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-041.