Decoding Requirements for Infiltration of T ceLLs into solid tumors

This project aims to enhance T cell infiltration into pancreatic cancer by investigating chemokine regulation and T cell determinants, potentially improving immunotherapy efficacy.

Subsidie
€ 1.521.000
2023

Projectdetails

Introduction

Cancer immunotherapies that leverage T cell activities are transforming cancer treatment. Currently, enormous effort has been devoted to empowering T cells to recognize and attack tumor cells. In contrast, the trafficking of T cells into tumors, a crucial prerequisite and limiting factor for effective T cell–tumor cell interactions, receives relatively less attention while at the same time being poorly understood. This is due to the complex and dynamic nature of T cell trafficking and the lack of model systems that allow function-based systematic investigation of the specific process.

Project Overview

This proposal integrates innovative functional genomics into physiologically relevant models that recapitulate two essential steps in the migration of effector T cells into tumors to investigate:

  1. Chemokine production in the tumor microenvironment (TME)
  2. Chemotactic infiltration of T cells into tumors

Here we focus on one of the most devastating cancers, pancreatic ductal adenocarcinoma (PDAC), because it poses considerable physical and biochemical barriers that restrict the access of effector T cells to tumor cells and substantially resists all available therapies.

Research Objectives

We will:

  1. Elucidate the (co)regulatory mechanisms of the expression of chemokines that direct T cell recruitment and exclusion.
  2. Develop model systems to systematically reveal cell-intrinsic determinants in T cells that influence their capability to infiltrate tumors.
  3. Evaluate whether pharmacological or genetic targeting of the modulators of T cell trafficking improves T cell-based cancer immunotherapies.

Expected Outcomes

Collectively, this project will deliver fundamental insight into the mechanisms that regulate T cell trafficking into tumors and may yield novel strategies to broaden or increase the efficacy of the current cancer immunotherapies.

Financiële details & Tijdlijn

Financiële details

Subsidiebedrag€ 1.521.000
Totale projectbegroting€ 1.521.000

Tijdlijn

Startdatum1-1-2023
Einddatum31-12-2027
Subsidiejaar2023

Partners & Locaties

Projectpartners

  • DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERGpenvoerder

Land(en)

Germany

Vergelijkbare projecten binnen European Research Council

ERC Advanced...

Developing novel single-cell technologies to model and perturb intra-tumor interactions and signaling – an innovation program for the next generation of immunotherapies

The TROJAN-Cell project aims to engineer immune responses against tumors by understanding immune-suppressive mechanisms in the tumor microenvironment using advanced single-cell technologies.

€ 2.500.000
ERC Consolid...

Unlocking a T cell-mediated Immune response in therapy-challenged Tumors

UnlockIT aims to develop mechanism-based combination therapies for cancer by understanding tumor-immune interactions and enhancing T cell responses in therapy-challenged tumors.

€ 2.000.000
ERC Starting...

Elucidating the networks of immune stromal connections by Perturbation of Immunity in Cancer - towards developing novel therapeutic strategies

This project aims to map immune and stromal cell interactions in the tumor microenvironment to develop targeted therapies that enhance immunotherapy efficacy against cancer.

€ 1.500.000
ERC Starting...

Understanding the functional role of Immune-related Intercellular Signalling Networks during tissue Development and Cancer

This project aims to uncover immune-related intercellular crosstalk in tissue development and cancer using single-cell RNA-sequencing and functional assays to identify novel therapeutic targets.

€ 2.025.000
ERC Starting...

Spatial Quantification of Cellular Metabolism in the Tumor Immune Microenvironment

This project aims to enhance cancer immunotherapy by quantifying immune cell metabolism in tumors to identify therapeutic targets that improve patient responses to treatment.

€ 1.497.756

Vergelijkbare projecten uit andere regelingen

EIC Pathfinder

Functional chemical reprogramming of cancer cells to induce antitumor immunity

The RESYNC consortium aims to revolutionize cancer immunotherapy by reprogramming cancer cells into antigen-presenting dendritic cells using small molecules for personalized and safer treatments.

€ 2.966.695