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. Author manuscript; available in PMC: 2020 Mar 1.
Published in final edited form as: Cancer Discov. 2019 Jul 2;9(9):1288–1305. doi: 10.1158/2159-8290.CD-19-0161

Figure 3. iαβTs protect against PDA and enhance intra-tumoral T cell immunity.

Figure 3.

(a) WT mice were administered KPC tumor cells subcutaneously, either alone or admixed with iαβTs. Tumor growth was serially measured (n=5/group). (b) WT mice were administered KPC tumor cells subcutaneously, either alone or admixed with PDA-infiltrating iαβTs. On day 21, tumor-infiltrating CD8+ T cells were analyzed for expression of TNFα (n=5/group). (c-f) WT mice were orthotopically administered KPC tumor cells, either alone or admixed with iαβTs. Tumors were harvested on day 21. (c) Representative pictures of tumors and quantitative analysis of tumor weight are shown. (d) PDA-infiltrating CD4+ and CD8+ T cells were analyzed for expression of CD44, (e) ICOS, and (f) TNFα (n=5/group). Each mouse experiment was repeated more than 3 times. (g-j) Mice with established orthotopic KPC tumor were serially transferred i.v. twice weekly with iαβTs or vehicle beginning on day 5 (n=5). Mice were sacrificed at day 21 after tumor implantation. (g) Representative pictures of tumors and quantitative analysis of tumor weight are shown. (h) PDA-infiltrating CD4+ and CD8+ T cells were analyzed for expression of CD44, (i) ICOS, and (j) IFNγ. Subcutaneous and orthotopic tumor experiments were each repeated at least 4 times. (k-m) Mice with established orthotopic KPC tumor were serially transferred i.v. twice weekly with iαβTs or vehicle beginning on day 5. Mice were sacrificed at day 21 and single cell RNAseq performed on FACS-purified CD45+ tumor-infiltrating leukocytes. (k) The distribution of cellular clusters was determined using the t-SNE algorithm. Each cluster is identified by a distinct color. (l) A t-SNE plot overlay of tumor-infiltrating leukocytes in tumors of mice treated with iαβTs (red) vs vehicle (blue) is shown. Percent cellular abundance in each cluster is depicted in pie charts and specified in the accompanying legend. (m) Violin plots comparing normalized log expression of select genes in the T cell cluster for both treatment groups are shown. (n) PDOTS derived from resected human tumors were treated with autologous iαβTs or vehicle. At 72h, CD8+ T cells were analyzed for expression of CD44, ICOS, IFNγ, and TNFα. Data is indicated as fold change in the iαβT cell-treated group compared to vehicle-treatment (n=5 patients; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001).