RT Journal Article
SR Electronic
T1 Cisplatin Augments Antitumor T-Cell Responses Leading to a Potent Therapeutic Effect in Combination With PD-L1 Blockade
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1749
OP 1760
DO 10.21873/anticanres.13281
VO 39
IS 4
A1 DAIKO WAKITA
A1 TOSHIKI IWAI
A1 SUGURU HARADA
A1 MIHO SUZUKI
A1 KANAME YAMAMOTO
A1 MASAMICHI SUGIMOTO
YR 2019
UL http://ar.iiarjournals.org/content/39/4/1749.abstract
AB Background: Immune checkpoint inhibitors have marked antitumor effect. However, monotherapy benefits only a limited population of patients, and further improvement of their effects is required. Here the therapeutic effect and immune response during anti-PD-L1 plus cisplatin combination therapy were investigated in a mouse model. Materials and Methods: E.G7-OVA, expressing ovalbumin (OVA) gene as a model tumor antigen, was subcutaneously inoculated into syngeneic mice and treated with anti-PD-L1 with/without cisplatin. The tumor growth and activation status of immune cells were evaluated. Results: The anti-PD-L1 plus cisplatin combination resulted in a potent antitumor effect leading to tumor shrinkage compared to anti-PD-L1 or cisplatin alone, even though each alone, significantly inhibited tumor growth compared to the control group. During treatment, all groups, including that treated with cisplatin alone, had increased CD8+ T-cell infiltration into tumor tissues compared with the control group, and the therapeutic effect was diminished by CD8+ cell depletion. Aside from its direct cytotoxic effect, cisplatin alone increased chemokine levels and expression of immune checkpoint molecules on CD8+ T-cells in the tumor site. The combination effectively activated OVA-specific CD8+ T-cells. Furthermore, anti-PD-L1 alone and in combination with cisplatin, but not cisplatin alone, induced interferon-gamma-producing CD4+ T-cells. Conclusion: These findings provide a rationale for anti-PD-L1 plus cisplatin becoming a promising combination therapy for patients with cancer.