While researchers often focus on CD8+ T cells in antitumor immunity, many studies have shown critical roles for CD4+ T cell responses as well. In order to better understand the context in which antitumor CD4+ T cell responses are initiated, Binnewies and Mujal et al. examined a variety of cell types and factors in tumors and tumor-draining lymph nodes (tdLNs) and explored possible therapeutic interventions to enhance the magnitude and quality of CD4+ T helper 1-like responses in both mice and humans.
Binnewies and Mujal et al. began by using single-cell RNAseq (scRNAseq) to characterize myeloid cells from tdLNs from B16F10 melanoma-bearing mice. From this data, they identified multiple clusters of both resident and migratory conventional dendritic cells (cDCs). In particular, they focused on two clusters, which bore a migratory cDC2 signature (Zbtb46, FLT3) and could be distinguished as either CD301b+ or CD301b-. The CD301b+ cDC2 subset expressed markers associated with cells of a monocyte/macrophage lineage and high levels of inhibitory receptors such as PD-L2. In a separate in vivo experiment, both subsets showed the capacity to bear tumor antigen and migrate in a CCR7-dependent manner from the tumor to the tdLN. These migratory cDC2 populations were found to be essential for the proliferation of transferred tumor-specific CD4+ T cells (OVA-specific OT-II cells). Ex vivo coculturing of either cDC2 subset with OT-II cells induced OT-II expansion, suggesting that the cDC2 subsets have overlapping function as inducers of antitumoral CD4+ T cell priming.