New insights into chronic inflammation-induced immunosuppression

Julia Kanterman, Moshe Sade-Feldman, Michal Baniyash*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

165 Scopus citations

Abstract

Chronic inflammation is a common factor linking various pathologies that differ in their etiology and physiology such as cancer, autoimmune diseases, and infections. At a certain stage of each of these diseases, while the chronic inflammation proceeds, some key players of the immune system become immunosuppressed as natural killer (NK) cells and T cells. The suppressive environment induced during chronic inflammation is governed by a complex processes characterized by the accumulation and activation of immune suppressor cells, pro-inflammatory cytokines, chemokines, growth and angiogenic factors, and by the activation of several inflammatory signaling pathways mediated predominantly by NFκB and STAT3 transcription factors. A substantial body of evidence supports the notion that the development of a suppressive environment during chronic inflammation limits the success of immune-based and conventional therapies, skewing the balance in favor of a developing pathology. Thus, appropriate, well-designed and fine tuned immune interventions that could resolve inflammatory responses and associated immunosuppression could enhance disease regression and reinforce successful responses to a given therapy. This review describes the interrelationship between chronic inflammation and induced immunosuppression, and explains the current evidence linking inflammation and pathological processes, as found in cancer. We further highlight potential strategies, harnessing the immunosuppressive environment in treating autoimmune diseases and facilitating transplantation. In parallel, we emphasize the use of modalities to combat chronic inflammation-induced immunosuppression in cancer, to enhance the success of immune-based therapies leading to tumor regression. In both cases, the urgent necessity of identifying biomarkers for the evaluation of host immune status is discussed, with the goal of developing optimal personalized treatments.

Original languageAmerican English
Pages (from-to)307-318
Number of pages12
JournalSeminars in Cancer Biology
Volume22
Issue number4
DOIs
StatePublished - Aug 2012

Bibliographical note

Funding Information:
We gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center , the Concern Foundation of Los Angeles and the Harold B. Abramson Chair in Immunology . This study was supported by the US-Israel Binational Science Foundation , The Israel Academy of Sciences and Humanities , The Israeli Ministry of Health , The Israel Cancer Research Foundation (ICRF) , The Joint German-Israeli Research Program (DKFZ) , and by The Joseph and Matilda Melnick Funds .

Keywords

  • Autoimmune diseases
  • Cancer
  • Chronic inflammation
  • Immunosuppression
  • Immunotherapy
  • Transplantation biomarkers

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