Understanding the Biology of Antigen Cross-Presentation for the Design of Vaccines Against Cancer

Abstract

Antigen cross-presentation, the process in which exogenous antigens are presented on MHC class I molecules, is crucial for the generation of effector CD8+ T cell responses. Although multiple cell types are being described to be able to cross-present antigens, in vivo this task is mainly carried out by certain subsets of dendritic cells (DCs). Aspects such as the internalization route, the pathway of endocytic trafficking, and the simultaneous activation through pattern-recognition receptors have a determining influence in how antigens are handled for cross-presentation by DCs. In this review, we will summarize new insights in factors that affect antigen cross-presentation of human DC subsets, and we will discuss the possibilities to exploit antigen cross-presentation for immunotherapy against cancer.

Vaccine delivery by penetratin: mechanism of antigen presentation by dendritic cells

“…Alternatively, AntpOVA can directly translocate into the cytoplasm followed by the proteolysis in the endoplasmic reticulum and Golgi compartments for loading into class I molecules in a TAPindependent mode. Our mechanistic data agrees with that of Lu et al [30] which demonstrates that TAT containing antigens can utilise alternative antigen presentation pathways bypassing the requirement for proteasomal processing and TAP dependence by proteolytic trimming in ER and Golgi compartments [30,70,71].…”

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

“…In preclinical studies, both IDO inhibitors were in effective attenuating tumor growth in wild type, but not immunodeficient animals. 111 Inhibitors of cyclooxygenase (COX) An immunosuppressive COX-2 product PGE2 is secreted abundantly by tumor cells and by tumor-infiltrating macrophages. Selective COX-2 inhibitors celecoxib and rofecoxib and a non-selective agent indomethacin have shown promising results not only in the treatment of primary tumors but also in the prevention of metastatic spread in both preclinical models and clinical settings.…”

Crystal Structure of Insulin-Regulated Aminopeptidase with Bound Substrate Analogue Provides Insight on Antigenic Epitope Precursor Recognition and Processing

“…The cross-presentation pathway is key for the immune defense against many viruses, bacteria, and tumors and can help the immune system avoid immune evasion strategies. Furthermore, cross-presentation is important for inducing cytotoxic responses through vaccination, especially against tumors (3,4).…”