# Investigating nanotube-mediated mitochondria transfer and inhibitor effects in cancer-immune cell interactions across 2D and 3D models

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $259,550

## Abstract

Project Summary/Abstracts
This supplementary project aims to uncover the mechanisms and implications of mitochondria transfer between
immune cells and cancer cells via tunneling nanotubes (TNTs), specifically focusing on the potential of inhibiting
these transfers to boost the efficacy of immunotherapies against cancer. Through the development and
application of 2D and 3D models, the study intends to explore how these mitochondrial transfers affect cancer
cell behavior across various macrophage phenotypes under different experimental conditions. A central goal of
the research is to assess the effectiveness and safety of nanotube inhibitors, thus providing new insights into
their potential to enhance current immune checkpoint therapies by disrupting TNT-mediated interactions between
cancer and immune cells.
Structured into three aims, the project will first characterize mitochondria trafficking between cancer cells and
macrophages via TNTs, focusing on the influence of macrophage phenotypes on cancer cell fate. This aim is
critical for understanding the nanotube-mediated mechanisms that cancer cells may use to evade immune
responses, potentially undermining the effectiveness of immune checkpoint inhibitors. The second aim will
develop 3D models that more accurately mimic physiological conditions for studying TNT dynamics than
traditional 2D models. This is vital for gaining insights into the unique structural and functional properties of TNTs
in 3D environments, especially regarding their interactions with the extracellular matrix (ECM) and its significant
impact on TNT formation and functionality. The final aim evaluates the efficacy of various nanotube inhibitors,
including those targeting the exocyst complex, in preventing TNT formation and mitochondrial transfer between
cancer cells and macrophages. This includes examining the effects of these inhibitors on macrophage immune
responses to cancer cells, with the overarching objective of enhancing anti-cancer immune activities in 3D
models.
This project addresses the gap in understanding the role of macrophages in immune responses to cancer cells,
particularly focusing on nanotube-mediated mitochondrial transfer and its implications for immune evasion. By
exploring these interactions in various 2D and 3D settings, the research aims to uncover novel insights into the
dynamically-changing structural and functional characteristics of TNTs. This understanding is expected to aid in
creating targeted therapies that enhance immune checkpoint inhibitor efficacy, contributing to the advancement
of cancer immunotherapy strategies.

## Key facts

- **NIH application ID:** 11062923
- **Project number:** 3R01CA276525-02S2
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Shiladitya Sengupta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $259,550
- **Award type:** 3
- **Project period:** 2023-07-19 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11062923

## Citation

> US National Institutes of Health, RePORTER application 11062923, Investigating nanotube-mediated mitochondria transfer and inhibitor effects in cancer-immune cell interactions across 2D and 3D models (3R01CA276525-02S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11062923. Licensed CC0.

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