TIM-4 Glycoprotein-Mediated Degradation of Dying Tumor Cells by Autophagy Leads to Reduced Antigen Presentation and Increased Immune Tolerance

Abstract Background Epigenetic mechanisms regulate chromatin accessibility patterns that govern interaction of transcription machinery with genes and their cis-regulatory elements. Mutations that affect epigenetic mechanisms are common in cancer. Because epigenetic modifications are reversible many anticancer strategies targeting these mechanisms are currently under development and in clinical trials. Main body Here we review evidence suggesting that epigenetic therapeutics can deactivate immunosuppressive gene expression or reprogram tumor cells to activate antigen presentation mechanisms. In addition, the dysregulation of epigenetic mechanisms commonly observed in cancer may alter the immunogenicity of tumor cells and effectiveness of immunotherapies. Conclusions Therapeutics targeting epigenetic mechanisms may be helpful to counter immune evasion and improve the effectiveness of immunotherapies.

Download Full-text

Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade

Annual Review of Cancer Biology ◽

10.1146/annurev-cancerbio-070220-111016 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Annette Paschen ◽

Ignacio Melero ◽

Antoni Ribas

Keyword(s):

Antigen Presentation ◽

Tumor Cells ◽

Mhc Class I ◽

Cancer Biology ◽

Interleukin 2 ◽

Interferon Γ ◽

Class I ◽

Annual Review ◽

Publication Date ◽

Type I

Resistance to immunotherapy is due in some instances to the acquired stealth mechanisms of tumor cells that lose expression of MHC class I antigen–presenting molecules or downregulate their class I antigen–presentation pathways. Most dramatically, biallelic β2-microglobulin (B2M) loss leads to complete loss of MHC class I expression and to invisibility to CD8+ T cells. MHC class I expression and antigen presentation are potently upregulated by interferon-γ (IFNγ) in a manner that depends on IFNγ receptor (IFNGR) signaling via JAK1 and JAK2. Mutations in these molecules lead to IFNγ unresponsiveness and mediate loss of recognition and killing by cytotoxic T lymphocytes. Loss of MHC class I augments sensitivity of tumor cells to be killed by natural killer (NK) lymphocytes, and this mechanism could be exploited to revert resistance, for instance, with interleukin-2 (IL-2)-based agents. Moreover, in some experimental models, potent local type I interferon responses, such as those following intratumoral injection of Toll-like receptor 9 (TLR9) or TLR3 agonists, revert resistance due to mutations of JAKs. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Download Full-text

Neuroimmunology for the Non-Immunologist

Neuroimmunology ◽

10.1093/med/9780190050801.003.0002 ◽

2019 ◽

pp. 2-20

Author(s):

Bibiana Bielekova

Keyword(s):

Immune System ◽

Antigen Presentation ◽

Immune Tolerance ◽

Short Introduction ◽

Immune Synapse ◽

Immune Systems ◽

Adaptive Immune ◽

Adaptive Immune Systems ◽

Autoimmune Phenomena

The chapter begins with a short introduction to the components of the immune system, outlining both the innate and adaptive components. It discusses the role of the immune system in protecting against infections and abnormal tissues. It describes the concepts of self-antigens, antigen presentation, and immune synapse. It then examines immune tolerance and the differing functions and capacities of the innate and adaptive immune systems. Finally, the chapter considers infections and autoimmune phenomena and how the immune system responds to these challenges.

Download Full-text

Multifunctional biomimetic nanoparticles loading baicalin for polarizing tumor-associated macrophages

Nanoscale ◽

10.1039/c9nr03353j ◽

2019 ◽

Vol 11 (42) ◽

pp. 20206-20220 ◽

Cited By ~ 8

Author(s):

Shulan Han ◽

Wenjie Wang ◽

Shengfang Wang ◽

Shuo Wang ◽

Ruijun Ju ◽

...

Keyword(s):

Immune System ◽

Tumor Cells ◽

Immune Tolerance ◽

Drug Efficacy ◽

Tumor Associated Macrophages ◽

Biomimetic Nanoparticles

Immunosuppression and immune tolerance lead tumor cells to evade immune system surveillance and weaken drug efficacy.

Download Full-text

Abstract 637: The class I HDAC inhibitor mocetinostat augments checkpoint inhibitor therapy via direct up regulation of antigen presentation transcriptional programs in tumor cells and increased T-cell clonality in tumors

10.1158/1538-7445.am2017-637 ◽

2017 ◽

Author(s):

David M. Briere ◽

Niranjan Sudhakar ◽

Peter Olson ◽

Jamie Christensen

Keyword(s):

T Cell ◽

Antigen Presentation ◽

Tumor Cells ◽

Hdac Inhibitor ◽

Checkpoint Inhibitor ◽

Inhibitor Therapy ◽

Class I ◽

Checkpoint Inhibitor Therapy ◽

T Cell Clonality ◽

Cell Clonality

Download Full-text

Deficient Major Histocompatibility Complex Class II Antigen Presentation in a Subset of Hodgkin's Disease Tumor Cells

Blood ◽

10.1182/blood.v92.7.2252 ◽

1998 ◽

Vol 92 (7) ◽

pp. 2252-2259 ◽

Cited By ~ 25

Author(s):

Herbert Bosshart ◽

Ruth F. Jarrett

Keyword(s):

Major Histocompatibility Complex ◽

Antigen Presentation ◽

Tumor Cells ◽

Mhc Class Ii ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Class Ii ◽

Histocompatibility Complex ◽

Class Ii Antigen ◽

Mhc Class Ii Molecules

Abstract Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II–associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease–derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II αβ dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II–restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.

Download Full-text