# Study of Anti-Tumor Immunity and Tissue Resident Memory Cell Development by NKG2D and Ribosomal Protein S6 Signaling in T cells

> **NIH NIH R01** · H. LEE MOFFITT CANCER CTR & RES INST · 2023 · $369,216

## Abstract

In the field of tumor immunology, while the generation and maintenance of anti-tumor CD8 T cell
memory responses are considered crucial for the long-term host survival, the basic tenets of memory
formation remain to be established. We propose to study and manipulate the CD8 T cell
NKG2D/DAP10  ribosomal protein S6 (rpS6) pathway as a means to generate durable and protective
anti-tumor immunity. The scientific premise of this study is derived from our work demonstrating that
NKG2D signaling provides CD8 T cells with pro-memory signals. We hypothesize that NKG2D,
through finely tuned DAP10PI3K/Grb2 signaling (as NKG2D cannot signal by itself, instead uses
DAP10PI3K/Grb2 as signaling adaptor), activates rpS6 resulting in the development of functionally
capable CD8 memory T cells. This proposal will define the underlying players required for rpS6
phosphorylation downstream of NKG2D/DAP10 and its implications in the development of
immunological memory against tumors including TRM cells. Here we will conduct proof-of-concept
tests utilizing human and mouse tumors, with the intention of preparing for a clinical trial.
SA1: TO DETERMINE THE MOLECULAR CONTRIBUTORS OF NKG2D-DAP10 INDUCED
PHOSPHORYLATION OF rpS6
SA2. TO DETERMINE THE ROLE OF NKG2D/DAP10PI3K/GRB2 IN THE DEVELOPMENT OF
TRADITIONAL MEMORY RESPONSES AND SKIN TRM CELLS AGAINST MELANOMA.
SA3. TO EVALUATE THE THERAPEUTIC POTENTIAL OF MANIPULATING THE
DAP10/rpS6 PATHWAY IN CD8 T CELLS

## Key facts

- **NIH application ID:** 10555239
- **Project number:** 5R01CA250514-05
- **Recipient organization:** H. LEE MOFFITT CANCER CTR & RES INST
- **Principal Investigator:** Jose Alejandro Guevara-Patino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $369,216
- **Award type:** 5
- **Project period:** 2021-07-14 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10555239

## Citation

> US National Institutes of Health, RePORTER application 10555239, Study of Anti-Tumor Immunity and Tissue Resident Memory Cell Development by NKG2D and Ribosomal Protein S6 Signaling in T cells (5R01CA250514-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10555239. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*