Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer

Abstract

Background: B and T lymphocyte attenuator (BTLA) is a co-signaling protein belonging to the CD28 immunoglobulin superfamily. However, the role of BTLA in prognosis and immunotherapy of colorectal cancer (CRC) remains unclear. Methods: We evaluated the expression of BTLA via the Oncomine and the cancer genome atlas (TCGA) database. We research the outcome among different BTLA expression patients by Kaplan-Meier curve. We used the Chi-Squared test and Cox regression analysis to identify potential risk factors. Besides, the correlations between BTLA and cancer immune infiltration were investigated via CIBERSORT. Results: Various cohorts showed that BTLA expression was lower in CRC compared to corresponding normal tissue. Moreover, low BTLA expression was correlated with poor overall survival in TCGA cohorts and Gene Expression Omnibus cohorts (GSE29623 and GSE17536). Low BTLA expression was associated with less lymph node metastasis (p = 0.0123). In the Cox proportional hazards model, BTLA was identified as a favorable prognostic factor. Naive B cells, memory B cells, CD8 T cells, CD4 memory resting T cells, follicular helper T (Tfh) cells, monocytes, resting natural killing (NK) cells, M0 macrophages, M1 macrophages, resting mast cells, and activated mast cells were affected by BTLA expression (all p < 0.01). Correlated immune markers and functional enrichment analysis revealed BTLA functioned in the T cell receptor signaling pathway, B cell receptor signaling pathway, and NK cell-mediated cytotoxicity pathway. Conclusion: These analyses suggest BTLA is a potential factor for extended survival and closely related to CD8 T cells, Tfh cells, B cells, and NK cells in CRC. We summarize these results that BTLA can be used as a prognostic biomarker and might contribute to developing novel CRC immunological treatment strategies.

Comprehensive Analysis of Glycolysis-Related Genes for Prognosis, Immune Features, and Candidate Drug Development in Colon Cancer

“…Analysis of immune cell infiltration revealed a significant difference between the risk groups, suggesting that abnormal glycolysis metabolism could alter the immune microenvironment, which could affect prognosis and treatment. A prior study (Song and Wu, 2020) reported an association between decreased infiltration of CD4+ memory resting T cells and poor prognosis. Other studies reported a rapid transformation of resting dendritic cells to activated dendritic cells under in vivo stimulation and their participation in adaptive immune responses (Joffre et al, 2009).…”

Tumor Mutation Burden and Immune Invasion Characteristics in Triple Negative Breast Cancer: Genome High-Throughput Data Analysis

“…Compared with the wild group, the FAT3 mutant group had more T cells and CD4 memory resting cells in immune cell infiltration and lower levels of activated NK cells and resting dendritic cells. In research data, resting memory CD4+ T cells are often associated with prognosis of malignant tumor diseases, such as bladder cancer (43), head and neck squamous cell carcinoma (44), and colorectal cancer (45), and it is speculated that FAT3 mutations are related to the infiltration state of resting memory CD4 + T cells, activated NK cells, and resting dendritic cells in triple-negative breast cancer. In addition, in the FAT3 mutation group, a correlation was found between the abundance of various immune cells and TMB level, TMB and immune cell infiltration are closely related to the pathological activities of tumor cells and are related to the prognosis of patients.…”

Roles of BTLA in Immunity and Immune Disorders

“…For instance, as suggested by Song et al, BTLA levels decreased in colorectal cancer tissues in comparison with levels in matched non-carcinoma tissues. In addition, decreased BTLA levels predicted poor overall survival and less LNM ( 53 ). Notably, BTLA is suggested to trigger both inhibitory and survival signaling, and may have a context-specific function in TILs ( 7 ).…”