Mapping Immune Correlates and Surfaceome Genes in BRAF Mutated Colorectal Cancers

Autor: Esther Cabañas Morafraile, Cristina Saiz-Ladera, Cristina Nieto-Jiménez, Balázs Győrffy, Adam Nagy, Guillermo Velasco, Pedro Pérez-Segura, Alberto Ocaña
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Current Oncology, Vol 30, Iss 3, Pp 2569-2581 (2023)
Druh dokumentu: article
ISSN: 30030196
1718-7729
1198-0052
DOI: 10.3390/curroncol30030196
Popis: 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.
Databáze: Directory of Open Access Journals
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