DCs pulsed with hypochlorous acid-treated tumor cell lysates present antigens efficiently and induce CD8+ T cell activation through cross-presentation.

Abstract

Background and purpose: In initiating and regulating immune responses, dendritic cells (DCs) play an important role as antigen-presenting cells. When DCs are exposed to tumor cell lysates, they can stimulate T cells to recognize tumor-associated and tumor-specific antigens and generate an immune response against cancer. The purpose of this study was to compare 4 different approaches for preparing breast tumor cell lysates for pulsing DCs.

Experimental approach: To prepare tumor cell lysates from 4T1 cells, 4 different methods were used, including freeze-thaw, hypochlorous acid (HOCl), hyperthermia, and ultraviolet-B irradiation. The effects of the tumor lysates were assessed on the maturation of DCs and the secretion of cytokines using flow cytometry and ELISA. Furthermore, DCs pulsed with different lysates were also evaluated for their ability to promote CD8+ T cell proliferation and release cytokines.

Findings/results: The results demonstrated that DCs pulsed with lysate prepared by HOCl exhibited more maturation surface biomarker expression (CD86) than DCs pulsed with freeze-thawed cells or unloaded DCs (control). Furthermore, activated DCs were also found to promote CD8+ T cell proliferation and induce the responses of T cells by producing high levels of IFN-γ, while inhibiting IL-10.

Conclusion and implications: HOCl is capable of releasing tumor antigens while maintaining its ability to stimulate an immune response. DCs-based therapies may be designed based on the findings presented here, demonstrating a cross-presentation of antigens and specific activation of the immune system against breast cancer.