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Updated: Aug 5, 2025
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Mapping Immune Correlates and Surfaceome Genes in BRAF Mutated Colorectal Cancers
Esther Cabañas Morafraile1,2, Cristina Saiz-Ladera2, Cristina Nieto-Jiménez2
1Center for Biological Research Margarita Salas (CIB-CSIC), Spanish National Research Council, 28040 Madrid, Spain.
Abstract:
Despite the impressive results obtained with immunotherapy in several cancer types, a significant fraction of patients remains unresponsive to these treatments. In colorectal cancer (CRC), B-RafV600 mutations have been identified in 8-15% of the patients. In this work we interrogated a public dataset to explore the surfaceome of these tumors and found that several genes, such as GP2, CLDN18, AQP5, TM4SF4, NTSR1, VNN1, and CD109, were upregulated. By performing gene set enrichment analysis, we also identified a striking upregulation of genes (CD74, LAG3, HLA-DQB1, HLA-DRB5, HLA-DMA, HLA-DMB, HLA-DPB1, HLA-DRA, HLA-DOA, FCGR2B, HLA-DQA1, HLA-DRB1, and HLA-DPA1) associated with antigen processing and presentation via MHC class II. Likewise, we found a strong correlation between PD1 and PD(L)1 expression and the presence of genes encoding for proteins involved in antigen presentation such as CD74, HLA-DPA1, and LAG3. Furthermore, a similar association was observed for the presence of dendritic cells and macrophages. Finally, a low but positive relationship was observed between tumor mutational burden and neoantigen load. Our findings support the idea that a therapeutic strategy based on the targeting of PD(L)1 together with other receptors also involved in immuno-modulation, such as LAG3, could help to improve current treatments against BRAF-mutated CRC tumors.
Insights
BRAF-mutated colorectal cancer (CRC) shows upregulated immune-related genes, including those for antigen presentation and checkpoint inhibitors like PD(L)1 and LAG3. Targeting these may improve immunotherapy response in CRC patients.
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.
