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. 2024 Apr 17;15(4):322–338.e5. doi: 10.1016/j.cels.2024.03.004

Figure 7.

Figure 7

Lymph nodes are sustained sources of T cells in the tumor microenvironment based on dendritic cell antigen presentation

(A) Schematic of added components to the model. We add dendritic cells that start in the tumor microenvironment and take up tumor antigen from dying tumor cells and are activated by tumor debris. Lymph nodes (LNs) migrate to the tumor-draining lLN (tdLN) where they can encounter tumor-specific T cells. Upon engagement between MHC-I and TCR of the T cells, T cells proliferate within the LN and leave the LN to the tumor microenvironment.

(B–D) Comparing simulations with added dendritic cells and LN processes vs. simulations without LN and dendritic cells: (B) total number of T cells, (C) total number of tumors, and (D) number of tumor cells separated by phenotype over the time course of the simulation. For (B)–(D), mean of n = 8 replicates with shading showing SEM.

(E) Comparison simulations of tumors treated with 25% PD-1+ T cells simulated with either a timer or a probabilistic T cell activation and refractory timing mechanism and showing total number of T cells separated by phenotype over simulation time (n = 5–8 replicates with shading showing SEM). This was done with code on an experimental branch (probabilistic-refractory) of tumor T cell repository.

(F) Representative CODEX images of tdLNs from B16-F10 tumors from mice treated on day 10 with activated PMEL therapeutic T cells (of either 25% PD-1+ T cells, 75% PD-1+ T cells) and harvested 3 days following treatment. Scale bar, 250 mm.

(G) PD1 median fluorescent signal across all CD8+ T cells within tdLNs or LNs or the tumors from mice treated with 25% PD-1+ T cells, 75% PD-1+ T cells, or no T cells (n = 2¬3 replicates with error bars showing SEM).

(H) Representative images of cell types mapped to LN tissues that correspond to figure G images.

(I) Cell type percentages from CODEX multiplexed imaging data of the tdLN of mice treated with either 25% PD-1+ T cells or 75% PD-1+ T cells 3 days post therapy (n = 4 replicates with error bars showing SEM).

(J) Model of T cells supported by immune cells in a microenvironment within the tumor for preservation of phenotype, proliferation, killing, and tumor inhibition locally.