Regulation of tumor antigens-Dependent immunotherapy via the hybrid M1 macrophage/tumor lysates Hydrogel.

ABSTRACT

Tumor treatment poses a significant obstacle in contemporary healthcare. Using components derived from a patient's own cellular and tissue materials to prepare hydrogels and other therapeutic systems has become a novel therapeutic approach, drawing considerable interest for their applicability in basic research on cancer immunotherapy. These hydrogels can engage with cellular components directly and offer a supportive scaffold, aiding in the normalization of tumor tissues. Additionally, their superior capability for encapsulating targeted anti-tumor medications amplifies treatment effectiveness. Given their origin from a patient's own cells, these hydrogels circumvent the risks of immune rejection by the body and severe side effects typically associated with foreign substance. In this study, we developed a composite hydrogel constructed by the cellular lysates of autologous tumor cells and M1 macrophages. This combination promoted the M2 macrophages polarization to the M1 phenotype. Subsequently, the polarized M1 macrophages infiltrated into the hydrogel and can directly capture tumor antigens. As antigen-presenting cells, M1 macrophages can stimulate the production of antigen-specific T cells to kill tumor cells. This work proposes a dual-benefit research strategy that not only polarizes M2 macrophages but also enhances immune activation, boosting T cell-mediated tumor-killing effects. This approach offers a new therapeutic option for clinical cancer immunotherapy.