Tumor-Infiltrating B Cells and Tissue-Resident Memory T Cells as Prognostic Indicators in Brain Metastases Derived from Gastrointestinal Cancers.

Simple Summary: This study identified tumor-infiltrating B cells (TIBs) and tissue-resident memory T cells (TRMs) as potential prognostic indicators in brain metastases (BMs) derived from gastrointestinal (GI) cancers. Higher densities of TIBs and TRMs in the BM tissues significantly correlated with improved overall survival after BM diagnosis. These findings suggest that quantifying TIB and TRM levels in surgically resected BM samples could provide valuable prognostic information to guide treatment decisions and follow-up strategies for patients with this lethal condition. Additionally, we revealed distinct spatial distributions and characteristics of these lymphocyte subsets, which advanced our understanding of the BM immune microenvironment. Further studies with larger cohorts are needed to validate these findings and explore their potential therapeutic implications. Background/Objectives: Tumor-infiltrating B cells (TIBs) and tissue-resident memory T cells (TRMs) play significant roles in antitumor immunity. However, their prognostic relevance in brain metastases (BMs) derived from gastrointestinal (GI) cancers remains unclear. This study aimed to investigate the prognostic significance of TIBs and TRMs in GI cancer-derived BMs (GIBMs). Methods: Retrospective histopathological analyses were performed on surgically resected GIBM tissues from 13 patients. The densities of tumor-infiltrating lymphocytes (TIL) subsets (TIBs, CD4+ T cells, CD8+CD103+ TRMs, and CD8+CD103- non-TRMs) were quantified and correlated with clinical parameters and overall survival (OS) including the Graded Prognostic Assessment (GPA). Results: TIBs and CD4+ T cells were predominantly accumulated in the tumor stroma, particularly around blood vessels, where they formed lymphocyte clusters without characteristics of tertiary lymphoid structures (TLSs). In contrast, TRMs more deeply infiltrated into the tumor epithelium than their counterpart non-TRMs. Positive correlations were found between TIB density and both the prognostic prediction of GPA and overall survival (OS) after BM diagnosis or surgery. Furthermore, increased densities of TIBs and TRMs were associated with enhanced survival after BM diagnosis. Conclusions: TIB and TRM densities in BM tissues could serve as reliable prognostic indicators for survival in patients with GIBMs. This study provides crucial insights for the development of novel immunotherapeutic strategies against this lethal disease. [ABSTRACT FROM AUTHOR]