Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure.

Selena Vigano,George Coukos,Matthieu Perreau,Alexandre Harari,Sara Bobisse

doi:10.3389/fimmu.2020.01350

Abstract

The main role of the human immune system is to eliminate cells presenting foreign antigens and abnormal patterns, while maintaining self-tolerance. However, when facing highly variable pathogens or antigens very similar to self-antigens, this system can fail in completely eliminating the anomalies, leading to the establishment of chronic pathologies. Prototypical examples of immune system defeat are cancer and Human Immunodeficiency Virus-1 (HIV-1) infection. In both conditions, the immune system is persistently exposed to antigens leading to systemic inflammation, lack of generation of long-term memory and exhaustion of effector cells. This triggers a negative feedback loop where effector cells are unable to resolve the pathology and cannot be replaced due to the lack of a pool of undifferentiated, self-renewing memory T cells. In addition, in an attempt to reduce tissue damage due to chronic inflammation, antigen presenting cells and myeloid components of the immune system activate systemic regulatory and tolerogenic programs. Beside these homologies shared between cancer and HIV-1 infection, the immune system can be shaped differently depending on the type and distribution of the eliciting antigens with ultimate consequences at the phenotypic and functional level of immune exhaustion. T cell differentiation, functionality, cytotoxic potential and proliferation reserve, immune-cell polarization, upregulation of negative regulators (immune checkpoint molecules) are indeed directly linked to the quantitative and qualitative differences in priming and recalling conditions. Better understanding of distinct mechanisms and functional consequences underlying disease-specific immune cell dysfunction will contribute to further improve and personalize immunotherapy. In the present review, we describe relevant players of immune cell exhaustion in cancer and HIV-1 infection, and enumerate the best-defined hallmarks of T cell dysfunction. Moreover, we highlight shared and divergent aspects of T cell exhaustion and T cell activation to the best of current knowledge.

Highlights

The primary function of the human immune system is to protect the host by reacting upon the encounter of foreign antigens, as well as to prevent autoimmunity through self-recognition
After CD8 T cell expansion and antigen elimination, any further immune activation is prevented by the upregulation and engagement of co-inhibitory molecules such as Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and Programmed Death1 (PD-1)
The combination of transcriptomic and proteomic data allowed the identification of multiple cell clusters that were evolving with Human Immunodeficiency Virus-1 (HIV-1) disease progression or initiation of ART [64]. These data may lead to the understanding of new specific features of disease evolution and drive novel therapeutic approaches

Summary

Introduction

The primary function of the human immune system is to protect the host by reacting upon the encounter of foreign antigens, as well as to prevent autoimmunity through self-recognition. Landmark studies in LCMV [67] and SIV/HIV-1 infection [33, 34, 62, 171, 172] highlighted the relevance of multiple ICs co-expression (i.e., CD160, 2B4, TIM3, T cell immunoreceptor with Ig and ITIM domains-TIGIT, CTLA-4 and LAG-3) to define deeply exhausted virus-specific CD8 T cells.

Results

Conclusion