Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination
Abstract
While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 17, 2023
- Source ID
- 10.1038/s41467-023-42303-5
Entities
People
- Addanki P Kumar
- Che-wei Hsu
- Cheryl Hsiang-Ling Chiu
- Chia-nung Hung
- Chien-Chin Chen
- Chih‐Wei Chou
- Chiou‐Miin Wang
- Chun-Liang Chen
- Chun-Lin Lin
- Gopalrao V N Velagaleti
- Josephine A. Taverna
- Kexin Xu
- Maria Gaczyńska
- Meizhen Chen
- Michael A Liss
- Moawiz Saeed
- Nameer B. Kirma
- Nathaniel Alvarez
- Pawel A. Osmulski
- Tim H-M Huang
- Veronica Ortega
- Xi Tan
- Zhao Lai
- Zhao Zhang
- Zhijie Liu
Organizations
- Cancer Prevention and Research Institute of Texas
- Foundation for the National Institutes of Health
- United States Department of Defense