Targeting Immune Cells May Help Address Treatment Resistance in Bladder Cancer

Overcoming treatment resistance in muscle-invasive bladder cancer (MIBC) may require targeting not only cancer cells, but also the immune cells that help them survive.

Although the treatment landscape for MIBC is rapidly evolving, cisplatin-based chemotherapy remains an important component of perioperative therapy, yet many tumors persist after treatment.

Understanding how cancer cells interact with their surrounding immune microenvironment may reveal new ways to overcome resistance and improve treatment responses.

Researchers from Mass General Brigham and Dana-Farber Cancer Institute, led by first author Filipe de Carvalho, MD, PhD, and senior author Eliezer Van Allen, MD, analyzed tumors from 14 patients whose cancers either responded to or resisted cisplatin-based chemotherapy.

Using single-cell and spatial technologies, the team mapped gene activity and cell-to-cell interactions within human tumors to identify biological programs associated with treatment resistance, and then tested potential therapeutic targets in preclinical models.

The researchers found that cisplatin-resistant tumors contained aggressive cancer cell states associated with worse survival and were surrounded by tumor-associated macrophages expressing PARP14. These cancer cells and macrophages formed spatially organized niches and engaged in signaling interactions that may help tumors survive chemotherapy.

In mouse models of bladder cancer, blocking PARP14 reprogrammed macrophages toward an anti-tumor state, reduced tumor growth and increased sensitivity to cisplatin.

These findings identify PARP14 as a promising therapeutic target for disrupting the cooperation between cancer cells and macrophages that promotes cisplatin resistance.

More broadly, the study suggests that reprogramming the tumor immune microenvironment could provide a strategy for overcoming treatment resistance in MIBC as therapeutic options continue to expand.

Published in Cell Press Blue on August 20, 2026 | Read the paper: “Tumor-myeloid crosstalk drives therapy resistance in localized bladder cancer(opens in new tab)”

Summary reviewed by: Filipe de Carvalho, MD, PhD, lead author