STAT3 inhibition reduced PD‐L1 expression and enhanced antitumor immune responses. Issue 12 (13th May 2020)

• Record Type: Journal Article
• Authors: Jahangiri, Amirhossein; Dadmanesh, Maryam; Ghorban, Khodayar
• Is Part Of: Journal of cellular physiology. Volume 235:Issue 12(2020:Dec.)
• Page Start: 9457
• Page End: 9463
• Publication Date: 2020-05-13
• Subjects: colon cancer -- FLLL32 -- HCT‐15 -- PD‐L1 -- STAT3; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.29750
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Colon cancer is one the most common diagnosed cancers in America and Europe. Signal transducer and activator of transcription 3 (STAT3) in colon cancer is associated with proliferation of the tumor cells and suppression of immune responses. STAT3 activation upregulates the transcription of many suppressor genes, including programmed death‐ligand 1 (PD‐L1). This study was aimed to investigate the effect of STAT3 inhibition in a colon cancer cell line, HCT‐15, and particularly in presence of samples obtained from the patients suffering from colon cancer. In this project, the expression of PD‐L1 and apoptosis‐related proteins were assessed following STAT3 inhibition, using FLLL32, in HCT‐15 cells. To evaluate the effects of STAT3 inhibition on immune response, lymphocytes from 20 men with Stage III colon cancer and 20 healthy donors were cocultured with HCT‐15 cells in presence or absence of STAT3 inhibitor. Then, T regulatory (T‐reg) cell evaluation and intracellular cytokine staining (ICS) were performed using flowcytometry to assess the T‐reg and T helper (Th) subset cytokines following STAT3 inhibition. STAT3 inhibition suppressed PD‐L1 expression and induced apoptosis in HCT‐15 cells. The population of T‐reg cells in patients with colon cancer significantly decreased after treatment with STAT3 inhibitor. ICS revealed that STAT3 inhibition promotes Th1 protective immune responses. These findings suggest that STAT3 inhibition through either induction of apoptosis in the colon cancer cells and/or activation of efficient immune responses can lead to overcome cancer‐induced immune tolerance. Abstract : Signal transducer and activator of transcription 3 (STAT3) has a pivotal role in cancer microenvironment. In this study, we investigate the relationships between STAT3 and programmed death‐ligand 1 (PD‐1). We also assess the role of STAT3 in T helper (Th) subtypes cytokine expression.