Williams Cancer Institute



Myeloid cells play a crucial role in fostering effective antitumor immunity; even though they contribute to T cell immune evasion in cancer, they are adaptable and harbor antitumor potential.

A study, conducted by Wattenberg et al., and published in the journal Science Immunology in 2023, focuses on myeloid cells, which can promote immune evasion in cancer but also have antitumoral potential.

By simultaneously targeting myeloid activation molecules (Dectin-1 and CD40) in pancreatic cancer models through systemic therapies with β-glucan and agonistic antibodies, respectively, established tumors were eradicated, inducing immunological memory in models resistant to checkpoint inhibitors.
The antitumoral activity involved cDC1 and T cells but did not rely on classical T cell cytotoxicity or checkpoint blockade. Instead, CD40 activation boosted IFN-γ signaling mediated by T cells, converging with Dectin-1 activation to program macrophages and facilitate tumor responses.

This approach reveals that productive immune surveillance in pancreatic tumors resistant to checkpoint inhibition can be achieved through the coactivation of complementary myeloid signaling pathways.

Reference: Max M. Wattenberg, Heather Coho, Veronica M. Herrera, Kathleen Graham, Meredith L. Stone, Yuqing Xue, Renee B. Chang, Christopher Cassella, Mingen Liu, Shaanti Choi-Bose, Stacy K. Thomas, Hana Choi, Yan Li, Kelly Markowitz, Lauren Melendez, Michael Gianonne, Nandita Bose, Gregory L. Beatty, 17 November 2023, Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1, https://www.science.org/doi/10.1126/sciimmunol.adj5097?utm_source=sfmc&utm_medium=email&utm_content=alert&utm_campaign=IMMeToc&et_rid=162353465&et_cid=4989803

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