Fig. 5: The upregulation of PD-L1 post BNT162b2-based cancer therapy affects the therapeutic efficacy, whereas combinational therapy of BNT162b2 and anti-PD-L1 effectively enhances therapeutic efficacy.

a Experimental design for investigating the therapeutic efficacy of B16F10-derived exosomes and BNT162b2-transfected B16F10-derived exosomes (n = 5 in the PBS i.v. group, n = 6 in exosome treatment groups). b Photo of tumors from the treatment and control groups at the endpoint of the experiment described in a. c Tumor growth curves of the BNT162b2-transfected B16F10-derived exosomes intravenous treatment group vs the B16F10-derived exosomes intravenous treatment group vs intravenous PBS control group for the experiment described in a. d Tumor growth curves of the BNT162b2-transfected B16F10-derived exosomes treatment group, B16F10-derived exosomes treatment group, and PBS control group for the experiment described in a. e Representative immunofluorescent staining images of tumor-infiltrating PD-L1+Gr-1+ neutrophils. f Quantitative analysis of the percentage of tumor-infiltrating PD-L1+Gr-1+ neutrophils in total live cells by flow cytometry (n = 5 per group). g Quantitative analysis of the percentage of tumor-infiltrating PD-L1+Gr-1+ neutrophils in total neutrophils by flow cytometry (n = 5 per group). h Experimental design of the combinational therapy of BNT162b2 and anti-PD-L1 (n = 5 per group). i Photo of tumors from the mice in the BNT162b2 treatment group, BNT162b2 + anti-PD-L1 combinational treatment group, and control groups at the endpoint of the experiment described in h. j Tumor growth curves of treatment groups vs control groups for the experiment described in h. k Tumor growth curves of the intratumoral PBS control group, intratumoral BNT162b2 treatment group, intraperitoneal anti-PD-L1 treatment group, and intratumoral BNT162b2 + intraperitoneal anti-PD-L1 combinational treatment group for the experiment described in h. BNT i.m.-PBS i.t.-αIso i.p.: the mice with BNT162b2 intramuscular injections, PBS intratumoral injections, and isotype antibody (αIso) intraperitoneal injections. BNT i.m.-BNT i.t.-αIso i.p.: the mice with BNT162b2 intramuscular injections, BNT162b2 intratumoral injections, and isotype antibody (αIso) intraperitoneal injections. BNT i.m.-PBS i.t.-αPD-L1 i.p.: the mice with BNT162b2 intramuscular injections, PBS intratumoral injections, and anti-PD-L1 antibody intraperitoneal injections. BNT i.m.-BNT i.t.-αPD-L1 i.p.: the mice with BNT162b2 intramuscular injections, BNT162b2 intratumoral injections, and anti-PD-L1 antibody intraperitoneal injections. The time points of different administrations were shown in h. Scale bars, 20 μm in e.