Antigen cross-presentation and T-cell cross-priming in cancer immunology and immunotherapy

Area of Science:

• Immunology
• Cancer Biology
• Cellular Biology

Background:

• Dendritic cells (DCs) are professional antigen-presenting cells crucial for adaptive T-cell responses.
• Cancer cells present tumor antigens but lack sufficient antigen presentation and costimulatory signals for T-cell priming.
• Antigen transfer to DCs and their presentation on MHC molecules are vital for antiviral and anticancer immunity.

Purpose of the Study:

• To highlight the role of specific dendritic cell subsets in cancer immunity.
• To explore the potential of enhancing dendritic cell function for cancer immunotherapy.

Main Methods:

• Review of existing literature on dendritic cell subsets and antigen presentation in cancer.
• Analysis of the function of BATF3/IRF8-dependent conventional DCs type 1 (cDC1s) in cross-presentation.
• Examination of the correlation between cDC1 location and T-cell infiltration in tumors.

Main Results:

• Conventional DCs type 1 (cDC1s) are particularly effective at cross-presenting tumor-associated antigens.
• The presence of cDC1s within tumors correlates with enhanced CD8+ T cell infiltration and tumor-specific immunity.
• cDC1s are essential for antitumor responses mediated by checkpoint inhibitors and agonistic antibodies in preclinical models.

Conclusions:

• Enhancing T-cell cross-priming by cDC1s presents a promising avenue for improving cancer immunotherapy.
• Strategies to increase cDC1 numbers, activation, and priming capacity within tumors are under investigation.
• Targeting tumor antigens to cDC1s via internalizing receptors could boost antitumor immunity.