Mapping Immune Correlates and Surfaceome Genes in BRAF Mutated Colorectal Cancers

Area of Science:

• Immunology
• Oncology
• Genetics

Background:

• Immunotherapy has shown promise in various cancers, but many patients do not respond. Colorectal cancer (CRC) with BRAF V600 mutations presents a challenge for current treatments.
• BRAF V600 mutations occur in 8-15% of CRC patients, highlighting a specific subset that may benefit from targeted therapies.

Purpose of the Study:

• To investigate the surfaceome and immune landscape of BRAF-mutated colorectal cancer (CRC).
• To identify potential therapeutic targets for improving immunotherapy response in this patient group.

Main Methods:

• Analysis of a public dataset of BRAF-mutated CRC tumors.
• Gene set enrichment analysis to identify upregulated pathways.
• Correlation analysis between gene expression, immune cell infiltration, and tumor mutational burden.

Main Results:

• Upregulation of several surfaceome genes (e.g., GP2, CLDN18, AQP5) and genes involved in antigen processing and presentation via MHC class II (e.g., CD74, LAG3, HLA molecules).
• Strong correlation between PD1/PD(L)1 expression and antigen presentation genes (CD74, HLA-DPA1, LAG3).
• Association of immune gene expression with dendritic cells and macrophages; low positive correlation between tumor mutational burden and neoantigen load.

Conclusions:

• BRAF-mutated CRC exhibits a distinct immune profile with upregulated antigen presentation machinery and immune checkpoint-related genes.
• Combined targeting of PD(L)1 and other immunomodulatory receptors like LAG3 may enhance immunotherapy efficacy in BRAF-mutated CRC.