Mismatch Repair-Proficient Colorectal Cancer Can Evade Immune Surveillance through an Intrinsic Suppressive Program.

MSS colorectal cancers evade immune responses through intrinsic secretome-driven mechanisms, despite identical antigen presentation to MSI tumors.

• Why it matters: Understanding how MSS-CRC bypasses immune surveillance is crucial because these tumors are resistant to immune checkpoint inhibitors, limiting treatment options beyond MSI-CRC.
• What they did: The study engineered a model with MSI- and MSS-CRC cells expressing the same antigen, then analyzed immune responses, secretome effects, and surface glycosylation alterations using mass spectrometry.
• The result: MSS tumors suppressed T-cell activation and cytotoxicity via secretome-mediated impairment of immune synapse formation, suggesting targeting glycosylation pathways could enhance immunotherapy in MSS-CRC.