Williams Cancer Institute

Unveiling the Tumor’s Stealth Strategy: How Cancer Blocks the Immune System in Metastasis

Cancer’s ability to spread to vital organs like the lungs often spells a grim prognosis for patients. A recent discovery sheds light on a cunning tactic employed by metastatic tumors, revealing why some promising immunotherapies may fall short in combating cancer’s deadly spread.

Research led by Dr. Kebin Liu, a cancer immunologist at the Medical College of Georgia, unveils a critical insight into cancer-associated fibroblast activation, a phenomenon that enables tumors to manipulate the body’s immune response. This manipulation often renders conventional immunotherapies ineffective, highlighting the need for innovative therapeutic strategies.

One key player in this immunoescape is the PD-L1 protein, which cancer cells exploit to evade immune detection. The PD-L1 binds to the PD-1 protein on immune cells called T cells, effectively putting the brakes on their ability to attack cancer cells. Drugs like Keytruda and OPDIVO aim to disrupt this interaction, unleashing the T cells’ killer instinct.

However, the study reveals a more intricate interplay at play, particularly in the context of cancer metastasis. Metastatic tumor cells directly engage with PD-1 on myeloid cells, a type of immune cell that can both activate and inhibit T cell responses. This engagement suppresses the production of type 1 interferon, a critical signaling molecule that recruits killer T cells to target cancer cells.

The findings underscore the need for targeted interventions that go beyond disrupting PD-L1/PD-1 interactions. Dr. Liu’s team is exploring novel approaches to force tumor cells to express interferon, effectively turning the tables on cancer’s metastatic strategies.

The potential of type 1 interferon in enhancing immune responses within the tumor microenvironment is also highlighted. By understanding the intricate signaling pathways involved in immune evasion, researchers aim to develop more effective therapies for combating metastatic cancer and improving patient outcomes.

This groundbreaking research not only unveils the stealth tactics of metastatic tumors but also paves the way for targeted immunotherapies that could revolutionize cancer treatment strategies. As the quest for effective cancer therapies continues, insights from studies like these offer hope in the ongoing battle against cancer’s relentless spread.

Reference: Klement, J. D., Redd, P. S., Lu, C., Merting, A. D., Poschel, D. B., Yang, D., Savage, N. M., Zhou, G., Munn, D. H., Fallon, P. G., & Liu, K. March 13, 2023. Tumor PD-L1 engages myeloid PD-1 to suppress type I interferon to impair cytotoxic T lymphocyte recruitment. https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00033-8

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