Ludwig MSK’s Jedd Wolchok and Taha Merghoub led a team, including researchers from MSK, New York and Brussels, to explore transforming growth factor-β (TGFβ) production and activity in stroma-poor colon and melanoma tumor models. TGFβ is a cytokine that has multiple roles in healthy and cancerous tissues. In the former, it can subdue proliferation and programmed cell death, while in certain cancers, such as melanoma and breast cancer, its signaling can promote metastasis and compromise immune surveillance. To complicate matters further, there are three subtypes of TGFβ, each with distinct patterns of expression. So far, the expression of TGFβ and its inhibition within the tumor microenvironment has mainly been investigated in stroma-rich tumors. Taha, Jedd and their Ludwig MSK colleagues Aditi Gupta and Sadna Budhu reported in a November paper in Communications Biology that myeloid and dendritic cells are the main source of TGFβ1 in colon carcinomas and both TGFβ1 and TGFβ3 in melanoma. Targeting TGFβ1 in colon cancer, and either TGFβ1 or TGFβ3 in melanoma, delays tumor growth—apparently by enhancing the activity of CD8+ T cells that target tumors. Their analysis suggests that isoform specific TGFβ inhibition in stroma-poor tumors can alter the tumor microenvironment in favor of anti-tumor immunity, and the researchers showed that its combination with immune checkpoint blockade improved tumor control in mouse models.
This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).