Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

08 August 2018 : Clinical Research  

Targeting Interleukin-6 (IL-6) Sensitizes Anti-PD-L1 Treatment in a Colorectal Cancer Preclinical Model

Jibin Li1ABCDEF, Jian Xu1ABCDE, Xiaofei Yan1BCDE, Keer Jin1BCF, Wenya Li1CDEF, Rui Zhang1ABCDEFG*

DOI: 10.12659/MSM.907439

Med Sci Monit 2018; 24: CLR5501-5508

Abstract

BACKGROUND: Limited efficacy of immune checkpoint blockades was observed in clinical trials in colorectal (CRC) patients, especially in the microsatellite-stable patients. Interleukin-6 (IL-6) is critical in modeling immune responses in cancers. However, the effects of targeting IL-6 in combination with immune checkpoint blockades is unknown in CRC.

MATERIAL AND METHODS: In the present study, we investigated the profile of IL-6 expression in tumor tissues of CRC patient and we established CRC mouse models with various IL-6 expression levels using CT26 cells and MC38 cells. Effects of anti-IL-6 and anti-PD-L1 combination treatment were tested in these models.

RESULTS: A total of 105 CRC patients were included in this study, with 41 (39%) females and 64 (61%) males. Sixty patients showed IL-6 high expression and 45 patients showed IL-6 low expression. The patients with IL-6 high expression tended to have shorter survival (median survival time of 25.5 months) than the patients with IL-6 low expression (median survival time of 46 months, P value=0.013). In the CRC mouse models, tumors with IL-6 overexpression tended to grow faster than the tumors with IL-6 knockout. The numbers of CD8+ T cells and CD4+ T cells were decreased in IL-6 overexpressed tumors. On the contrary, myeloid-derived suppressor cells and regulatory/suppressor T cells were more numerous in tumors with IL-6 overexpression. PD-L1 expression was upregulated in the tumors with IL-6 overexpression. Importantly, an IL-6 blockade reversed the anti-PD-L1 resistance and prolonged tumor-bearing mouse survival.

CONCLUSIONS: Our study indicates that IL-6 induces strong immunosuppression in the CRC microenvironment by recruiting immunosuppression cells and impairing T cell infiltration. Inhibition of IL-6 enhanced the efficacy of anti-PD-L1 in CRC, providing a novel strategy to overcome anti-PD-L1 resistance in CRC.

Keywords: Antigens, CD274, Colorectal Neoplasms, Hereditary Nonpolyposis, Immunity, Cellular, Interleukin-6

0 Comments

Editorial

04 June 2022 : Editorial  

Editorial: Acute Hepatitis of Unknown Origin in Children. Is Autoimmunity at Play?

Nahum Mendez-Sanchez, Shreya C. Pal
Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico

DOI: 10.12659/MSM.937371

Med Sci Monit 2022; 28:e937371

SARS-CoV-2/COVID-19

30 June 2022 : Editorial  

Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Respo...

Med Sci Monit In Press; DOI: 10.12659/MSM.937676  

27 June 2022 : Clinical Research  

Shoulder Injury Related to Vaccine Administration (SIRVA) in 16 Patients Following COVID-19 Vaccination Who...

Med Sci Monit In Press; DOI: 10.12659/MSM.937430  

In Press

30 Jun 2022 : Laboratory Research  

Bcl-2 19-kDa Interacting Protein 3 (BNIP3)-Mediated Mitophagy Attenuates Intermittent Hypoxia-Induced Human...

Med Sci Monit In Press; DOI: 10.12659/MSM.936760  

30 Jun 2022 : Editorial  

Editorial: World Health Organization (WHO) Variants of Concern Lineages Under Monitoring (VOC-LUM) in Respo...

Med Sci Monit In Press; DOI: 10.12659/MSM.937676  

30 Jun 2022 : Clinical Research  

Antioxidant System and Ions Concentrations After Femoral Neck and Resurfacing Hip Arthroplasty

Med Sci Monit In Press; DOI: 10.12659/MSM.936335  

28 Jun 2022 : Meta-Analysis  

Urodynamics in Early Diagnosis of Diabetic Bladder Dysfunction in Women: A Systematic Review and Meta-Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.937166  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750