Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status.

Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status. Immunol Lett. 2019 Oct 03;: Authors: Ashizawa T, Iizuka A, Maeda C, Tanaka E, Kondou R, Miyata H, Sugino T, Kawata T, Deguchi S, Mitsuya K, Hayashi N, Asai A, Ito M, Yamaguchi K, Akiyama Y Abstract Recently, clinical studies using anti-immune checkpoint molecule antibodies have been successful in solid tumors, such as melanoma and non-small cell lung cancers. However, pancreatic cancers are still intractable and difficult to treat once recurrence or metastasis occurs; thus, novel combined use of immune checkpoint blockade (ICB) with molecular targeted drugs is considered a therapeutic option. Previously, we developed a novel humanized MHC-double knockout (dKO) NOG mouse model and demonstrated that an anti-PD-1 antibody or a STAT3 inhibitor showed anti-tumor effects through an immunological mechanism. In the current study, using a humanized mouse model, we aimed to develop a combination therapy with an anti-PD-1 antibody and a STAT3 inhibitor (STX-0119) for use in vivo against pancreatic cancer. In an in vitro investigation, STX-0119 showed weak to moderate cytotoxic activity against several pancreatic cancer cell lines, which exhibited activated pSTAT3 and weak PD-L1 expression. However, unexpectedly, an in vivo study indicated that the combination of the anti-PD-1 antibody with STX-0119 remarkably reduced the anti...
Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research