Work

Immunogenic clearance combined with PD-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8+ T cell

Year: 2024

Type: article

Abstract: • Immunogenic clearance increases proliferating CD8 + T cells. • Proliferating CD8 + T cells potentially differentiate into effector memory-like CD8 + T cells (Tem). • Tem were abundant in immune checkpoint blockade (ICB) responder. • Combining immunogenic clearance and ICB increase Tem, leading to better immune response and tumor clearance. Immune checkpoint inhibition shows promise for cancer treatment, but only a minority of patients respond. Combination strategies have been explored to overcome this resistance. Combining immunogenic clearance using immunogenic cell death inducers with a rho kinase inhibitor enhances phagocytosis of immunogenically dying cancer cells by antigen-presenting cells, stimulating tumor-specific immune responses by activating CD8 + T cells via dendritic cell-mediated priming. This approach increases the responsiveness of immune checkpoint blockade (ICB)-resistant cancer to ICB. However, the precise mechanisms remain unclear. This study elucidates cellular mechanisms of immunogenic clearance enhancing ICB response. Using single-cell RNA sequencing, we observed an increase in effector memory-like CD8 + T cells within the tumor microenvironment with combined treatment. We propose this cell cluster may originate from proliferating CD8 + T cells elevated by immunogenic clearance. Notably, abundant effector memory-like CD8 + T cells in ICB-responsive patients suggest their antitumor effect. Thus, increasing this cell population through enhanced T cell priming may improve the response of ICB-resistant tumors.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2024.102209