# Targeting the immunologic vulnerabilities of small cell lung carcinoma

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $15,969

## Abstract

PROJECT SUMMARY/ABSTRACT
This K08 proposal describes a five-year career development training program in tumor immunobiology. Dr. Navin
R. Mahadevan has completed clinical training in Anatomic and Molecular and Genetic Pathology at Brigham and
Women’s Hospital and Harvard Medical School (HMS), and will pursue this research program with the goal of
transitioning to an independent laboratory-based career investigating cell-intrinsic and -extrinsic mechanisms of
immune regulation in the tumor microenvironment, along with a minor component of clinical service in diagnostic
molecular pathology.
 In this training program, Dr. Mahadevan will develop further expertise in the study of tumor
immunogenicity, and acquire new skills in the areas of antigen discovery and high-resolution slide-based
expression profiling, which will critically inform his future studies. His mentor, Dr. David Barbie (Associate
Professor of Medicine at the Dana-Farber Cancer Institute and HMS), is an leader in the field of translational
tumor immunology with an excellent track record in mentoring trainees, including those who have successfully
become independent laboratory-based faculty at major academic centers. Dr. Mahadevan has also assembled
an Advisory Committee with complementary expertise in tumor immunology (Drs. Sharpe and Rodig),
epigenetics and immunotherapy (Dr. Uppaluri), and computational genomics (Dr. Van Allen), and extensive
experience in mentoring physician-scientists to independent careers. Dr. Mahadevan will further supplement his
training with didactic courses to deepen his scientific knowledge, leadership, and communication, and will
regularly present his work at national and international meetings.
 The primary objective of Dr. Mahadevan’s proposed research is to elucidate the immunologic
vulnerabilities of small cell lung carcinoma (SCLC). Dr. Mahadevan provides preliminary data identifying an
immunogenic subtype of SCLC that depresses MHC Class I (MHC I) antigen presentation and may be
responsive to immune checkpoint blockade in patients. This proposal will leverage this new understanding of
SCLC immunobiology to rationally elucidate immunologically vulnerabilities of these distinct SCLC subtypes.
 Immunologic and functional assays will be employed to test three independent but related questions
following from this hypothesis: (1) the tumor microenvironmental consequences of MHC I derepression by SCLC;
(2) the sensitivity of MHC I low SCLC to natural killer cell-mediated cytotoxicity; (3) the epigenetic regulation and
potential immunogenicity of MHC I-restricted antigens derepressed in MHC I high SCLC. These studies will lead
to a deeper understanding of distinct SCLC immunophenotypes and attendant anti-tumor immune responses,
which could lead to the identification of novel biomarkers and development of effective immunotherapies for this
treatment-refractory disease.

## Key facts

- **NIH application ID:** 10909154
- **Project number:** 5K08CA270077-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Navin Mahadevan
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $15,969
- **Award type:** 5
- **Project period:** 2022-09-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909154

## Citation

> US National Institutes of Health, RePORTER application 10909154, Targeting the immunologic vulnerabilities of small cell lung carcinoma (5K08CA270077-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909154. Licensed CC0.

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