# Investigating the interplay between senescence and T cell immunity

> **NIH NIH K99** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $143,275

## Abstract

PROJECT SUMMARY/ABSTRACT
CANDIDATE: One of my long-standing interests is to understand the mediators of a successful antitumoral T
cell response. In this application, I am proposing a series of studies where I combine my graduate study
background in T cell biology with the expertise of the laboratory of my mentor Dr. Scott Lowe in in vivo cancer
modeling and tumor suppression. My research in the Lowe lab at Memorial Sloan Kettering Cancer Center
(MSKCC) has focused on how senescence, a common consequence of conventional anticancer therapies,
affects the function of T cells. Here I am delineating a plan for transitioning to independence that will allow me
to: (i) complete a set of experiments that are leading to discoveries I will be able to continue exploring as an
independent investigator; (ii) Acquire a set of expertise and further develop a research line that will separate me
from my present and past mentors and (iii) develop a series of professional skills needed for leading a lab.
RESEARCH: Cellular senescence in cancer cells is a stress-induced program that results in stable cell cycle
arrest and in secretion of a plethora of cytokines that can affect the behavior of other cells, including immune
cells. Senescence has been shown to have an immunostimulatory or immunosuppressive role in different
contexts. Cellular senescence is a common outcome of antitumoral therapies, yet the precise mechanisms by
which senescence alters adaptive anti-tumor immune responses remain largely unexplored. This project aims at
studying the functional consequences of senescence on T cells, utilizing novel model of cancer I have developed.
In Aim 1, I will explore how different drivers of senescence can lead to a T cell-infiltrated or a T cell-excluded
tumor microenvironment. In Aim 2 I will explore how an immunostimulatory form of senescence affects the
functionality of T cells that are specific for senescent and non-senescent cancer cells. These studies will inform
on how senescence can affect an antitumoral T cell response and on how to rationally design better anticancer
senescence-inducing approaches.
ENVIRONMENT: MSKCC provides an ideal environment for me to accomplish my training and research goals,
and successfully transition to an independent faculty position at an academic institution. My mentor Dr. Lowe is
a world leader in cancer biology, with a particular expertise on tumor suppressor programs, mouse models, and
functional genetics. In addition, I have assembled an advisory committee of three established scientists with
relevant and complementary expertise and strong commitment to mentoring (Drs. Pe’er, Rudensky, and Rosen),
who will support my transition to independence by providing valuable research and career guidance. Together
with the collaborative environment and broad spectrum of resources at MSKCC, this support network creates
optimal conditions for the successful completion of the proposed research and career development plans.

## Key facts

- **NIH application ID:** 10898035
- **Project number:** 5K99CA279782-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Riccardo Mezzadra
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $143,275
- **Award type:** 5
- **Project period:** 2023-08-02 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898035

## Citation

> US National Institutes of Health, RePORTER application 10898035, Investigating the interplay between senescence and T cell immunity (5K99CA279782-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10898035. Licensed CC0.

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