Combined type 2 cytokine blockade enhances PD-1-mediated antitumor immunity
Year: 2026
Type: article
Abstract: Immune checkpoint inhibitors improve outcomes for many patients with cancer, but resistance remains a major clinical challenge. Type 2 cytokines, including IL-4, IL-13, and thymic stromal lymphopoietin (TSLP), have been implicated in suppressing anti-tumor immunity. Here, we investigated whether combined blockade of IL-4, IL-13, and TSLP enhances anti-tumor responses alone and in combination with PD-1 inhibition. IL-4 impaired T cell-mediated tumor control and reduced expression of immune-stimulatory molecules by monocyte-derived dendritic cells in vitro. In CT26 and KP787 tumor models, combined blockade of IL-4, IL-13, TSLP, and PD-1 improved tumor growth inhibition and was associated with reprogramming of T cells, monocytes, and dendritic cells toward anti-tumor phenotypes. Across multiple human cancer datasets, transcriptional signatures associated with IL-4/IL-13 and TSLP activity correlated with poorer survival. These findings identify type 2 cytokine signaling as a suppressive pathway in anti-tumor immunity and support its therapeutic targeting to enhance checkpoint inhibitor efficacy.
Source: Cell Reports
Authors: Thomas Fabre, Eleanore Hendrickson, Katherine McGourty, Paola M. Marcovecchio, James McMahon, Sara Patti, KaiLi Cage, Stephen Searles, Christella Widjaja, Christopher Stairiker, Kathryn Bound, Roxanne Martino, Edward Pyszczynski, Ying Zhang, Graham Thomas, Samuel A. Stoner, Keith A. Ching, Fang Jin, Christopher P. Dillon, Thomas A. Wynn, Alexander M.S. Barron, Richard L. Gieseck
Institution: Pfizer (United States)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W7204456338