Center for Molecular Medicine Cologne

Nguyen, Phuong-Hien | Renata Stripecke | Alessandro Annibaldi - A 09

Understanding the multifaceted regulation of T cell immunity in B cell lymphoma for improved immunotherapy

Introduction

Treatment for B cell malignancies has shifted towards a chemo-free regiment with the combination of targeted therapy and/or immunotherapy. However, resistance to these therapeutics has emerged and new complementary options are still urgently needed for these cases. Regulation of T cell activity and restoration of T cell-mediated anti-tumor responses represent a prime research focus for immunotherapy. However, tumor cells can employ various mechanisms to evade anti-tumor immune responses, leading to the failure of cytotoxic T cells to efficiently proliferate and form immunologic synapses. The deregulated expression of diverse immune checkpoint molecules as well as co-stimulatory receptors have been described to modulate the activation of major T cell subsets. Moreover, the modulating effect of stromal cells on lymphoma development and T cell activity has been increasingly acknowledged. Stromal cells not only contribute to tumor growth via the interdependent generation of a nurturing tumor niche, but also adopt a number of other immunosuppressive mechanisms to modulate immune responses resulting in an enhanced immune tolerance to the tumor.  

The main goal of this project is to understand the complex regulation of T cell immunity by both the stroma and lymphoma cells to develop new therapeutic combinations. Particularly, regimens combining targeted- and immunotherapies will be tested in different in vitro and in vivo models.

Clinical Relevance

The modulation of anti-lymphoma T cell activity is not fully elucidated. Understanding the multifaceted regulation of T cell responses by both malignant cells and the stromal microenvironment will provide more insights into the effectiveness as well as vulnerability of T cell-based immunotherapy for B cell lymphoma. Ultimately, our project seek to develop preclinically complementary therapies against lymphoma hindering immune-suppressions caused by stromal deregulations and T cell exhaustion.

Approach

  • Explore the molecular mechanisms underlying stroma-induced remodeling of T cell immunity and anti-tumor response.
  • Elucidate the adaptation of lymphoma cells during immunotherapy and their impacts on T cell phenotype and activity.
  • Test the potential of combined immunotherapy for improved B cell lymphoma treatment.
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Dr. Phuong-Hien Nguyen CMMC Cologne
Dr. Phuong-Hien Nguyen

Clinic I for Internal Medicine

CMMC - PI - A 09
CMMC - PI - CAP 19

Publications - Phuong-Hien Nguyen

Link to PubMed

Prof. Dr. Renata Stripecke CMMC Cologne
Prof. Dr. Renata Stripecke

Clinic I of Internal Medicine - Chair of Translational Immune-Oncology

CMMC - Co-PI - A 09

+49 221 478 51457

Clinic I of Internal Medicine - Chair of Translational Immune-Oncology

Weyertal 115c

50931 Cologne

https://innere1.uk-koeln.de/forschung/arbeitsgruppen-labore/translational-immune-oncology/

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Publications - Renata Stripecke

Link to PubMed

Dr. Alessandro Annibaldi CMMC Cologne
Dr. Alessandro Annibaldi

Center for Molecular Medicine Cologne | Lab. of Cell Death, Inflammation and Immunity - CMMC Research Building

CMMC - Co-PI - A 09
CMMC - PI - JRG 12

+49 221 478 37455

Center for Molecular Medicine Cologne | Lab. of Cell Death, Inflammation and Immunity - CMMC Research Building

Robert-Koch-Str. 21

50931 Cologne

https://www.annibaldi-lab.cmmc-uni-koeln.de

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Publications - Alessandro Annibaldi

Link to PubMed

Group Members

PhD students:
Liudmila Lobastova
Thanh-Tung Truong
Viktoria Kohlhas
Technician:
H. Bohner