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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Mechanisms of Immune Evasion and Immune Modulation by Lymphoma Cells
Thomas Menter1, Alexandar Tzankov1
1Institute of Pathology and Medical Genetics, University Hospital of Basel, Basel, Switzerland.
Purpose:
Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies.
Methods:
A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic.
Results:
We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28. The prototypical example of a lymphoma manipulating and thereby silencing the immune system is Hodgkin lymphoma. Also other lymphomas, e.g., primary mediastinal B-cell lymphoma and some Epstein-Barr virus (EBV)-driven malignancies, use analogous survival strategies, while diffuse large B-cell lymphoma of the activated B-cell type, follicular lymphoma and angioimmunoblastic T-cell lymphoma to name a few, exert further immune escape strategies each. These insights have already led to new treatment opportunities and results of the most important clinical trials based on this concept are briefly summarized. Immune checkpoint inhibition might also have severe side effects; the mechanisms of the rather un(der)recognized hematological side effects of this treatment approach are discussed.
Conclusion:
Silencing the host's immune system is an important feature of various lymphomas. Achieving a better understanding of distinct pathways of interactions between lymphomas and different immunological microenvironment compounds yields substantial potential for new treatment concepts.
Insights
Immune checkpoint inhibition, targeting CTLA4/B7 and PD1/PDL1 pathways, offers new therapeutic options for lymphomas by overcoming immune suppression. Understanding these interactions reveals novel treatment strategies and potential hematological side effects.
Area of Science:
- Oncology
- Immunology
- Hematology
Background:
- Cancer immunotherapy, particularly immune checkpoint inhibition, is a growing therapeutic modality for various malignancies.
- Targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA4)/B7 and programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PDL1) signaling pathways has shown success in hematologic malignancies.
Purpose of the Study:
- To provide a comprehensive overview of the pathophysiological role of immunosuppressive networks in lymphomas.
- To elucidate distinct signaling pathways and cellular microenvironment changes contributing to immune evasion in lymphomas.
- To summarize clinical trial outcomes and discuss potential hematological side effects of immune checkpoint inhibitors.
Main Methods:
- Literature review of PubMed.
- Compilation of own study results.
Main Results:
- Lymphomas, including Hodgkin lymphoma, primary mediastinal B-cell lymphoma, and EBV-driven malignancies, employ immunosuppressive networks to silence the host immune system.
- Specific immune escape strategies are utilized by various lymphoma subtypes, such as diffuse large B-cell lymphoma, follicular lymphoma, and angioimmunoblastic T-cell lymphoma.
- Insights into these interactions have led to new treatment opportunities, with clinical trial results summarized.
Conclusions:
- Immune system silencing is a key feature of numerous lymphomas.
- Understanding the interplay between lymphomas and the immune microenvironment offers significant potential for developing novel therapeutic strategies.
- Further research into immune checkpoint inhibition is warranted, including understanding and managing its hematological side effects.
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