Inducing effective anti-tumor immunity has become a major therapeutic strategy against cancer. Dendritic cells (DC) are a heterogenous population of antigen presenting cells that infiltrate tumors. While DC play a critical role in the priming and maintenance of local immunity, their functions are often diminished, or suppressed, by factors encountered in the tumor microenvironment. Furthermore, DC populations with immunosuppressive activities are also recruited to tumors, limiting T cell infiltration and promoting tumor growth. Anti-cancer therapies can impact the function of tumor-associated DC and/or alter their phenotype. Therefore, the design of effective anti-cancer therapies for clinical translation should consider how best to boost tumor-associated DC function to drive anti-tumor immunity. In this review, we discuss the different subsets of tumor-infiltrating DC and their role in anti-tumor immunity. Moreover, we describe strategies to enhance DC function within tumors and harness these cells for effective tumor immunotherapy.

The identification of the specific DC subsets providing a critical role in presenting influenza antigens to naïve T cell precursors remains contentious and under considerable debate. Here we show that CD8+ T lymphocyte (TCD8+) responses are severely hampered in C57BL/6 mice deficient in the transcription factor Batf3 after intranasal challenge with influenza A virus (IAV). This transcription factor is required for the development of lymph node resident CD8+ and migratory CD103+CD11b− DCs and we found both of these subtypes could efficiently stimulate anti-IAV TCD8+. Using a similar ex vivo approach, many publications on this subject matter excluded a role for resident, non-migratory CD8+ DC. We postulate the differences reported can partially be explained by how DC are phenotyped, namely the use of MHC class II to segregate subtypes. Our results show that resident CD8+ DC upregulate this marker during IAV infection and we advise against its use when isolating DC subtypes.

The question of which dendritic cells (DCs) cross-present peripheral tumor antigens remains unanswered. We assessed the ability of multiple skin-derived and lymphoid resident DCs to perform this function in a novel orthotopic murine melanoma model where tumor establishment and expansion is within the skin. Two migratory populations defined as CD103XCR1 and CD103XCR1 efficiently cross-presented melanoma-derived antigen, with the CD103XCR1 DCs surprisingly dominating this process. These results are critical for understanding how antitumor CD8 T cell immunity is coordinated to tumor antigens present within the skin.