# Assessment of Tim-4+ Pleural Macrophages as Negative Regulators of Anti-Tumor T Cell Immunity in Lung Cancer

> **NIH NIH K08** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $200,575

## Abstract

PROJECT SUMMARY/ABSTRACT
Research: Lung cancer is the leading cause of cancer death in the United States. The success of immune
checkpoint blockade (ICB) with antibodies to PD-(L)1 have been a remarkable clinical advance. However, the
majority of patients do not respond to ICB monotherapy and most of those who initially do respond eventually
succumb to the disease. Malignant pleural effusions represent a challenging clinical scenario that is associated
with poor prognosis and reduced responses to ICB. Preliminary data presented in this proposal demonstrates
that activated T cells surprisingly express phosphatidylserine despite remaining viable and cytotoxic. Moreover,
this expression of phosphatidylserine mediates susceptibility to phagocytic clearance by peritoneal
macrophages that express the phosphatidylserine receptor Tim-4. In addition, Tim-4 abrogation improves
responses to ICB in a murine model of peritoneal carcinomatosis. As pleural macrophages are ontogenically
and transcriptionally similar to their peritoneal macrophage counterpart, we hypothesize that Tim-4+ pleural
macrophages impart immunosuppression in malignant pleural effusions by clearing anti-tumor CD8+ T cells. In
this proposal, we will systematically characterize Tim-4+ macrophage-PShigh T cell interactions in both murine
and human models of malignant pleural effusion. Furthermore, we will explore whether Tim-4 blockade has the
potential to substantially enhance the efficacy of immunotherapy in lung cancer.
Candidate: Dr. Andrew Chow is a Medical Oncology Fellow in the Department of Medicine at Memorial Sloan
Kettering Cancer Center (MSKCC). He aims to become an independent, tenure-track physician-scientist
investigating Tim-4+ pleural macrophages as a novel therapeutic target to overcome resistance to
immunotherapies in lung cancer. Dr. Chow will conduct the proposed research under the mentorship of Drs.
Charles Rudin and Jedd Wolchok, who are internationally recognized experts in lung cancer and immunotherapy,
respectively. Dr. Chow has outlined a five-year period of mentored training that builds on his laboratory-based
skills in mouse modeling, flow cytometry, and microscopy and his clinical training in medical oncology. For the
next phase of mentored training, he will develop skills in single-cell RNA sequencing analysis, CAR T cell design
and manufacture, CRISPR-Cas9 editing, and clinical protocol writing. Dr. Chow has also assembled a well-
accomplished advisory committee composed of Drs. Sohrab Shah, Prasad Adusumilli, and Katherine Panageas,
who will help to guide his training and research.
Environment: MSKCC is the world's oldest and largest private cancer center, devoting more than 130 years to
exceptional patient care, innovative research, and outstanding educational programs. MSKCC exposes trainees
to an exceptionally robust academic research environment with a strong commitment and track record of
successfully supporting junior faculty who are seeking careers as ...

## Key facts

- **NIH application ID:** 9951429
- **Project number:** 1K08CA248723-01
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Andrew Chow
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,575
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9951429

## Citation

> US National Institutes of Health, RePORTER application 9951429, Assessment of Tim-4+ Pleural Macrophages as Negative Regulators of Anti-Tumor T Cell Immunity in Lung Cancer (1K08CA248723-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9951429. Licensed CC0.

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