Intratumoral STING activations overcome nagative impact of cisplatin on antitumor immunity by inflaming tumor microenvironment in squamous cell carcinoma （扁平上皮癌に対するシスプラチンとSTING活性化療法の併用に関する研究）
著者
原渕, 翔平
(Harabuchi, Shohei)
上位タイトル
Biochemical and Biophysical Research Communications
Vol.522,
No.2
(2020.
2)
,p.408-
414
識別番号
ISSN
0006-291X
DOI
10.1016/j.bbrc.2019.11.107.
その他
PMID: 31771883
博士論文情報
学位授与番号
10107A545
学位授与年月日
2020-03-25
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Although cisplatin (CDDP) has been used as a major chemotherapeutic drug for head and neck squamous cell carcinoma (HNSCC), its impact on T-cell functions is controversial. Therefore, we investigated the immunologic effects of CDDP and antitumor effects by combination therapy of CDDP with a ligand for stimulator of interferon genes, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Direct impacts of CDDP on T-cell functions were addressed by comparing T-cell functions between human subjects treated and untreated with CDDP. The immune responses and the efficacy of combination therapy using CDDP and cGAMP were assessed using BALB/c mice inoculated with mouse squamous cell carcinoma (SCC) cell lines. CDDP inhibited T-cell proliferation in a dose-dependent manner. T-cell functions of CDDP-treated HNSCC patients were comparable to those of healthy donors and CDDP-untreated HNSCC patients. In the mice bearing SCC cell lines, combination therapy using CDDP and cGAMP enhanced the gene expressions of CXCL9 and CXCL10 in the tumor tissues and inhibited tumor growth. The antitumor effect was cancelled by anti-CXCR3 monoclonal antibody. These findings suggest that the combination therapy using CDDP and an immunomodulating drug like cGAMP would be a rational cancer immunotherapy for patients with HNSCC.
