Sitravatinib potentiates immune checkpoint blockade in refractory cancer models

被引：94

作者：

Du, Wenting ^{[1
,2
]}

Huang, Huocong ^{[1
,2
]}

Sorrelle, Noah ^{[1
,2
]}

Brekkenu, Rolf A. ^{[1
,2
,3
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Surg, Div Surg Oncol, Dallas, TX USA

[2] Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, 6000 Harry Hines Blvd, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, Dallas, TX USA

来源：

JCI INSIGHT | 2018年 / 3卷 / 21期

关键词：

RESISTANCE;

D O I：

10.1172/jci.insight.124184

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Immune checkpoint blockade has achieved significant therapeutic success for a subset of cancer patients; however, a large portion of cancer patients do not respond. Unresponsive tumors are characterized as being immunologically "cold," indicating that these tumors lack tumor antigen-specific primed cytotoxic T cells. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MerTK) and split tyrosine-kinase domain-containing receptors (VEGFR and PDGFR families and KIT) plus RET and MET, targets that contribute to the immunosuppressive tumor microenvironment. We report that sitravatinib has potent antitumor activity by targeting the tumor microenvironment, resulting in innate and adaptive immune cell changes that augment immune checkpoint blockade. These results suggest that sitravatinib has the potential to combat resistance to immune checkpoint blockade and expand the number of cancer patients that are responsive to immune therapy.

引用

页数：10

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