A recent study conducted by Mayo Clinic researchers has identified proteins linked to immunotherapy resistance in patients with metastatic colorectal cancer. The findings, published in Clinical Cancer Research, may provide insights into why some patients do not respond to this treatment.
Immunotherapy is considered a significant advancement in cancer treatment; however, it has been ineffective for many individuals with metastatic colorectal cancer. The research team discovered that specific proteins, fibronectin and smooth muscle actin, within the cancer tissues are associated with this resistance.
Dr. Frank Sinicrope, a medical oncologist and gastroenterologist at Mayo Clinic and the senior author of the study, emphasized the need for predictive biomarkers to guide immunotherapy selection. "Identifying those who may have resistance to treatment can be useful because then we can spare them from receiving treatment that may not be beneficial and could produce significant toxicities," he explained.
The research utilized digital spatial profiling technology to analyze multiple proteins' expression and their locations within tissues. This approach allowed the team to examine tumor environments closely, including interactions between proteins within and around tumor cells.
Dr. Sinicrope likened these spatial tools to an aerial view of a neighborhood: "Similarly, this detailed view provides physicians and researchers with critical information about the proteins in and around a patient's cancer."
The study focused on 10 regions at the invasive margin of tumors, applying digital spatial profiling to investigate 71 distinct proteins in both epithelial and stromal compartments of tumors. Fibronectin and smooth muscle actin were identified as extracellular matrix proteins present in the epithelial region associated with resistance to immunotherapy.
Further analysis indicated that cancer-associated fibroblasts produced these proteins, potentially suppressing the anti-tumor immune response. The discovery represents progress toward more personalized colorectal cancer treatments.
For additional details on authorship, disclosures, and funding sources related to this study, readers are encouraged to review the full publication.
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