Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice
| العنوان: | Combined treatment with HMGN1 and anti-CD4 depleting antibody reverses T cell exhaustion and exerts robust anti-tumor effects in mice |
|---|---|
| المؤلفون: | Haru Ogiwara, Francis H. W. Shand, Shiro Shibayama, Chang Yu Chen, De Yang, Shoji Yokochi, Yoshiro Ishiwata, Satoshi Ueha, Joost J. Oppenheim, Kouji Matsushima, Shungo Deshimaru, Shigeyuki Shichino |
| المصدر: | Journal for Immunotherapy of Cancer Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-13 (2019) |
| بيانات النشر: | BioMed Central, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, CD4-Positive T-Lymphocytes, Cancer Research, T cell, Immunology, CD8-Positive T-Lymphocytes, lcsh:RC254-282, Antibodies, Flow cytometry, High mobility group nucleosome binding protein 1 (HMGN1), 03 medical and health sciences, 0302 clinical medicine, Immune system, Cell Line, Tumor, Neoplasms, medicine, Immunology and Allergy, Animals, Pharmacology, Nucleosome binding, Combination cancer immunotherapy, Mice, Inbred BALB C, medicine.diagnostic_test, biology, Chemistry, CD137, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Recombinant Proteins, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Anti-CD4 depleting antibody, Cancer research, biology.protein, Molecular Medicine, Female, Immunotherapy, Antibody, CD8, HMGN1 Protein, Research Article |
| الوصف: | Background Transient depletion of CD4+ T cells results in tumor suppression and survival benefit in murine models; however, the tumor progression and recurrence still occur over more long-term monitoring of mice. Thus, we explored an additional strategy to enhance endogenous immune responses by an alarmin, high mobility group nucleosome binding protein 1 (HMGN1). Methods The anti-tumor effects of HMGN1, anti-CD4 depleting antibody, and their combined treatment were monitored in the Colon26 or the B16F10 subcutaneous murine models. The tumor-infiltrating CD8+ T cell proliferation, differentiation, exhaustion, and its gene expression were determined by flow cytometry, transcriptome analysis, and quantitative real-time PCR. Results Our results show that a systemic administration of low doses of HMGN1 with an anti-CD4 depleting antibody (HMGN1/αCD4) promoted expansion of CD8+ T cell populations (e.g. CD137+ PD-1+ and CD44hi PD-1+), recruited CCR7+ migratory dendritic cells to the tumor, and reduced co-inhibitory molecules (e.g. PD-1, LAG-3, and TIM-3) to counteract CD8+ T cell exhaustion. Conclusion The HMGN1/αCD4 treatment expanded effector CD8+ T cells and prolonged their anti-tumor activities by rescuing them from exhaustion, thus resulting in tumor regression and even rejection in long-term monitored mice. Electronic supplementary material The online version of this article (10.1186/s40425-019-0503-6) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 2051-1426 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9f17052d34b82ff485447d85b3e60c0 http://europepmc.org/articles/PMC6352494 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b9f17052d34b82ff485447d85b3e60c0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20511426 |
|---|