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. Author manuscript; available in PMC: 2022 Mar 30.
Published in final edited form as: Nat Cancer. 2021 Sep 30;2(10):1071–1085. doi: 10.1038/s43018-021-00247-z

Figure 6.

Figure 6

Therapeutic vaccination and agonistic anti-CD40 are efficacious in low neoantigen expressing tumors. (a) Percent of total peripheral blood CD8+ T cells that are antigen specific (CD44+/SIINFEKL tetramer+) in loSIIN tumor-bearing mice following two weeks (two doses) of OVA250–270 (N = 8 animals), non-specific (N = 7 animals), or no peptide-based vaccination (N = 8 animals). (b) Flow plot of peripheral blood antigen-specific CD8+ T cells from OVA250–270 vaccinated mouse, representative of N = 8 animals. (c) Change in loSIIN tumor size as measured by longitudinal colonoscopy following 14 days (two doses) of OVA250–270 (N = 8 animals) or non-specific vaccination (N = 7 animals). Significance assessed by Wilcoxon Rank Sum of percent change in tumor size. (d) Primary tumor sizes at necropsy 28 days post-vaccine regimen initiation. N = 10 OVA250–270 and 7 non-specific vaccine treated animals. Significance assessed by Wilcoxon Rank Sum. (e-j) Immunotherapy preclinical trial of mice bearing loSIIN tumors showing change in tumor size after 14 days of treatment, as determined by colonoscopy. N = 18 (e), 12 (f), 12 (g), 16 (h), 12 (i), and 12 (j) independent animals. Significance assessed by Wilcoxon Rank Sum of percent change in tumor size of treatment groups versus no treatment, with Holm’s correction. (k-l) Colonoscopy images of tumors pre- and post-treatment from mice receiving no treatment (k) and αCD40/αPD-1/αCTLA-4 (l), representative of N = 18 and 17 animals, respectively. (m) Primary tumor sizes at necropsy 28 days post-treatment initiation. ACT = adoptive cell transfer of OT-1s. N = 21 no treatment, 12 αPD-1, 12 αCTLA-4, 15 αCD40, 12 αCD40/αPD-1, 12 αCD40/αCTLA-4, 17 αCD40/αPD-1/αCTLA-4, and 10 ACT arm animals. Significance assessed by Wilcoxon Rank Sum with Holm’s correction. (n) Fraction of mice with any metastases (liver, lung, or omentum). N = same as (m). Significance assessed by 2×2 Fisher’s exact test with Holm’s correction. (o-r) Stereoscopic images of primary colon tumor (o), liver (p), lung (q), and omental (r) metastases from an αPD-1-treated mouse 28 days post-treatment initiation, representative of N = 12 animals.