Figure 3. Targeting and mimicry of APCs to promote immunity against cancer.

A) Conventional paradigm for DC-based vaccines where innate immune populations are removed from a patient, conditioned ex vivo with factors like tumor lysate to promote maturation, the reintroduced to provide signals to the patient’s adaptive immune cells.⁵³. B-C) Artificial APCs that control the presentation of cytokines to T cells and D) incorporate T cell costimulatory factors to generate cytotoxic T cells.^55,56 This incorporation of T cell costimulatory factors in artificial APC scaffolds (APC-ms) at a range of loadings (A1-A4) was benchmarked against T cell activating Dynabeads administered at a range of doses (D1-D3). E) Combinatorial approach to switch TAMs toward immunogenic phenotype by including mannose binding sites on PLGA NPs that were loaded with drug and photosensitizers to control macrophage inflammation at specific sites.⁶³ F) Implanted biomaterials scaffolds are able to mature DC phenotypes in situ through recruitment and exposure to antigens, adjuvants, and chemokines.⁵². G) Presence of an implanted scaffold alone impacts the phenotype of TAMs, as demonstrated through gene expression analysis of TAM populations following a mock surgery (left column) or scaffold implantation (right column).⁶⁸ H) Implants for release of different drug combinations at tumor resection site were compared at Days 7 and 14 for the impact on MDSCs, TAMs (M2-like macrophages), and DCs.⁷⁰ Panels adapted with permission from the indicated references.