Calr inactivation potentiates CD8 ⁺ T cell–mediated antitumor response through the classical MHC-I antigen presentation pathway. (A–C) Tumor volumes of control and Calr-deficient LLC tumors in WT mice (A), WT mice treated with anti-NK1.1 depletion antibodies (B), and WT mice treated with anti-CD8 depletion antibodies (C) (n = 6–8 per group). Data are presented as the mean ± SEM and representative of two independent experiments. ns, not significant; ***P < 0.001; ****P < 0.0001 by two-way ANOVA. (D–F) Tumor volumes of control and Calr-deficient LLC tumors (D, n = 6–8 per group), MC38 tumors (E, n = 6–8 per group), and B16F10 tumors (F, n = 4–6 per group) in WT mice and Rag1 KO mice. Data are presented as the mean ± SEM and representative of two independent experiments. ns, not significant; *P < 0.05; ***P < 0.001; ****P < 0.0001 by two-way ANOVA. (G) Schematic diagram illustrating the outcomes resulting from B2m KO and H2-T23 KO. In B2m KO cells, both classical and nonclassical MHC-I molecules are defective. In H2-T23 KO, only the nonclassical MHC-I H2-T23 is defective. (H–J) Volume of control and Calr KO LLC tumors in H2-T23 KO LLC (H, n = 5–7 per group), H2-T23 KO MC38 (I, n = 6 per group), and H2-T23 KO B16F10 (J, n = 8–9 per group) tumors in WT C57BL/6 mice. Results are representative of two independent experiments. Data are presented as the mean ± SEM and analyzed by two-way ANOVA. *P < 0.05; ***P < 0.001; ****P < 0.0001. (K–M) Tumor volumes of control and Calr-deficient tumors in B2m KO LLC (K, n = 5–6 per group), B2m KO MC38 (L, n = 5–6 per group), and B2m KO B16F10 (M, n = 6 per group) tumors in WT mice. Data are presented as the mean ± SEM and representative of two independent experiments. ns, not significant by two-way ANOVA.