Intratumoral immunomodulation by myeloid cell-specific autophagy.

<p><b>(A)</b> Atg5^flox/flox or LysM-Atg5 ^-/- BMDM were exposed to irradiated EG7 cells for 2 h and then co-cultured with wild-type CD4⁺ or CD8⁺ T cells for 96 h. CD4⁺ T cells expressing IFN-γ, IL-4, IL-17 or Foxp3, as well as CD8⁺ T cells expressing granzyme-B (GZM-B) were assayed by flow cytometry. <b>(B)</b> B16-OVA cells were inoculated subcutaneously into LysM-Atg5^-/- or Atg5^flox/flox mice that had been adoptively transferred with OT-I cells. After tumors were established (~25 mm²), tumor-infiltrating lymphocytes were isolated from the tumor tissues 4 days after the final treatment of CDDP and analyzed for the expression of SIINFEKL/H-2Kb complex on TAM by flow cytometry. Representative dot plots (left) and statistical analysis (n = 4; right) are shown. (<b>C</b>) MC38 cells were injected into the spleens of Atg5^flox/flox or LysM-Atg5^-/- mice two days after intravenous administration of anti-CD8 Ab. Twenty-one days later, the mice were sacrificed and subjected to macroscopic analysis for metastatic lesions in the liver. Representative data (upper) and statistical analysis of average areas of metastatic lesions are shown (bottom). White arrows indicate metastatic tumor areas. *: <i>p</i><0.05, ns: not significant.