Tumor-Infiltrating Myeloid Cells Confer De Novo Resistance to PD-L1 Blockade through EMT-Stromal and Tgfβ-Dependent Mechanisms

Haocheng Yu; John P Sfakianos; Li Wang; Yang Hu; Jorge Daza; Matthew D Galsky; Harkirat S Sandhu; Olivier Elemento; Bishoy M Faltas; Adam M Farkas; Nina Bhardwaj; Jun Zhu; David J Mulholland

doi:10.1158/1535-7163.MCT-22-0130

Tumor-Infiltrating Myeloid Cells Confer De Novo Resistance to PD-L1 Blockade through EMT-Stromal and Tgfβ-Dependent Mechanisms

Mol Cancer Ther. 2022 Nov 3;21(11):1729-1741. doi: 10.1158/1535-7163.MCT-22-0130.

Authors

Haocheng Yu¹, John P Sfakianos², Li Wang^{1

3}, Yang Hu⁴, Jorge Daza², Matthew D Galsky⁵, Harkirat S Sandhu⁶, Olivier Elemento⁴, Bishoy M Faltas^{4

7}, Adam M Farkas⁸, Nina Bhardwaj⁸, Jun Zhu^{1

3}, David J Mulholland⁶

Affiliations

¹ Sema4, Stamford, Connecticut.
² Department of Urology, Icahn School of Medicine at Mount Sinai, New York, New York.
³ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York.
⁵ Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶ Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
⁷ Departments of Medicine, Cell and Developmental Biology, Weill Cornell Medicine, New York, New York.
⁸ Parker Institute of Cancer Immunotherapy, San Francisco, California.

Abstract

Most patients with bladder cancer do not respond to ICB targeting of the PD-L1 signaling axis. Our modeling applied a de novo resistance signature to show that tumor-infiltrating myeloid cells promote poor treatment response in a TGFβ-dependent mechanism.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

B7-H1 Antigen* / genetics
Humans
Lymphocytes, Tumor-Infiltrating
Myeloid Cells
Signal Transduction
Transforming Growth Factor beta
Tumor Microenvironment
Urinary Bladder Neoplasms*

Substances

B7-H1 Antigen
Transforming Growth Factor beta

Abstract

Publication types

MeSH terms

Substances

Grants and funding