# Tumor-Immune Interactions and Cisplatin Resistance in Bladder Cancer

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $210,973

## Abstract

Project summary
 This K08 Career Development Award proposal for Dr. Filipe de Carvalho describes a research plan and
career development program leading up to an academic career as an independent Urologic Oncologist surgeon-
scientist investigator. Dr. De Carvalho is a urologist at Brigham and Women’s Hospital committed to an
independent research career focused on accelerating the development of therapeutic strategies to target the
immune-suppressive tumor microenvironment in bladder cancer. This Career Development award will allow Dr.
De Carvalho to become proficient in tumor-associated macrophage biology in bladder cancer with the ultimate
goal of developing novel macrophage-directed therapeutic strategies for bladder cancer patients. Dr. De
Carvalho will be mentored by Dr. Eliezer Van Allen and co-mentors Drs. Kent Mouw and Elizabeth Mittendorf,
leaders in bladder cancer genomics and cancer immunology. Dr. Van Allen is Chief of Division of Population
Sciences, Dana-Farber Cancer Institute, and has mentored over a dozen of young investigators that moved to
successful independent academic positions. Dr. De Carvalho also gathered an outstanding scientific advisory
committee and collaborators that excel in mouse models, statistics and cancer genomics to guide career
development and scientific progress.
 The research proposal focuses on tumor-associated macrophages, which are immune cells with a critical
role in tumor growth and immune evasion. Recent evidence revealed a therapy-induced conversion of normally
anti-tumor TAMs to a tumor-permissive phenotype. The central hypothesis is that cisplatin induces chronic
immunosuppressive IFN signaling in cancer cells leading to a TAM-infiltrated phenotype and immune evasion in
treatment-resistant tumors. The central hypothesis will be tested by pursuing two specific aims: 1) Determine the
mechanism and effectiveness of targeting TAMs to improve sensitivity of bladder cancer to combined cisplatin
and immune checkpoint inhibition. 2) Dissect the tumor-TAM crosstalk that mediates cisplatin resistance. These
studies are expected to dissect how TAMs inhibit cytotoxic T-cells in cisplatin-resistant bladder cancer in
territories of immune evasion across bladder tumors as well as position Dr. De Carvalho to submit a competitive
R01 near the completion of this Award.

## Key facts

- **NIH application ID:** 10985089
- **Project number:** 1K08CA282969-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Filipe de Carvalho
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $210,973
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10985089

## Citation

> US National Institutes of Health, RePORTER application 10985089, Tumor-Immune Interactions and Cisplatin Resistance in Bladder Cancer (1K08CA282969-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10985089. Licensed CC0.

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