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Article ; Online: Tetracyclines enhance antitumor T-cell immunity via the Zap70 signaling pathway.

Tone, Mari / Iwahori, Kota / Hirata, Michinari / Ueyama, Azumi / Tani, Akiyoshi / Haruta, Jun-Ichi / Takeda, Yoshito / Shintani, Yasushi / Kumanogoh, Atsushi / Wada, Hisashi

Journal for immunotherapy of cancer

2024 Volume 12, Issue 4

Abstract: Background: Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer. Therefore, the development of novel cancer immunotherapy is anticipated. In preliminary studies, we demonstrated ... ...

Abstract	Background: Cancer immunotherapy including immune checkpoint inhibitors is only effective for a limited population of patients with cancer. Therefore, the development of novel cancer immunotherapy is anticipated. In preliminary studies, we demonstrated that tetracyclines enhanced T-cell responses. Therefore, we herein investigated the efficacy of tetracyclines on antitumor T-cell responses by human peripheral T cells, murine models, and the lung tumor tissues of patients with non-small cell lung cancer (NSCLC), with a focus on signaling pathways in T cells. Methods: The cytotoxicity of peripheral and lung tumor-infiltrated human T cells against tumor cells was assessed by using bispecific T-cell engager (BiTE) technology (BiTE-assay system). The effects of tetracyclines on T cells in the peripheral blood of healthy donors and the tumor tissues of patients with NSCLC were examined using the BiTE-assay system in comparison with anti-programmed cell death-1 (PD-1) antibody, nivolumab. T-cell signaling molecules were analyzed by flow cytometry, ELISA, and qRT-PCR. To investigate the in vivo antitumor effects of tetracyclines, tetracyclines were administered orally to BALB/c mice engrafted with murine tumor cell lines, either in the presence or absence of anti-mouse CD8 inhibitors. Results: The results obtained revealed that tetracyclines enhanced antitumor T-cell cytotoxicity with the upregulation of granzyme B and increased secretion of interferon-γ in human peripheral T cells and the lung tumor tissues of patients with NSCLC. The analysis of T-cell signaling showed that CD69 in both CD4 Conclusions: In conclusion, tetracyclines enhanced antitumor T-cell immunity via Zap70 signaling. These results will contribute to the development of novel cancer immunotherapy.
MeSH term(s)	Animals ; Mice ; Humans ; Carcinoma, Non-Small-Cell Lung ; CD8-Positive T-Lymphocytes ; Lung Neoplasms ; Minocycline/metabolism ; Minocycline/pharmacology ; Signal Transduction ; Lymphocyte Activation
Chemical Substances	Minocycline (FYY3R43WGO)
Language	English
Publishing date	2024-04-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-008334
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Article ; Online: Tetracyclines Enhance Anti-tumor T-Cell Responses Induced by a Bispecific T-Cell Engager.

Noguchi, Yuki / Yamamoto, Yoko / Iwahori, Kota / Matsumoto, Mitsunobu / Hirata, Michinari / Okuyama, Hiroomi / Shintani, Yasushi / Kumanogoh, Atsushi / Wada, Hisashi

Biological & pharmaceutical bulletin

2022 Volume 45, Issue 4, Page(s) 429–437

Abstract: Cancer immunotherapies are powerful therapeutic options for cancer patients. To enhance the therapeutic effects of cancer immunotherapies, we plan to develop novel immunostimulatory drugs for use in combination with cancer immunotherapy. In the present ... ...

Abstract	Cancer immunotherapies are powerful therapeutic options for cancer patients. To enhance the therapeutic effects of cancer immunotherapies, we plan to develop novel immunostimulatory drugs for use in combination with cancer immunotherapy. In the present study, we focused on tetracyclines, the effects of which are controversial for immunotherapy. We examined the effects of tetracyclines on human T cells in the peripheral blood of healthy donors and the tumor tissues of non-small cell lung cancer (NSCLC) patients. By using bispecific T-cell engager technology to assess the cytotoxicity of peripheral T cells against tumor cells, we showed that tetracyclines (minocycline, tetracycline, doxycycline, meclocycline, chlortetracycline, and demeclocycline) enhanced T-cell cytotoxicity through granzyme B expression and CD4+ and CD8+ T-cell proliferation. In analyses of the peripheral blood mononuclear cells (PBMCs) and lung tumor-infiltrated cells of NSCLC patients, we found that demeclocycline enhanced T-cell cytotoxicity not only in PBMCs, but also in lung tumor tissues. These results support the further application of tetracyclines to combination cancer immunotherapy.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Humans ; Leukocytes, Mononuclear ; Lung Neoplasms/drug therapy ; Minocycline ; T-Lymphocytes
Chemical Substances	Minocycline (FYY3R43WGO)
Language	English
Publishing date	2022-04-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b21-00806
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Article ; Online: S-531011, a Novel Anti-Human CCR8 Antibody, Induces Potent Antitumor Responses through Depletion of Tumor-Infiltrating CCR8-Expressing Regulatory T Cells.

Nagira, Yoji / Nagira, Morio / Nagai, Ryohei / Nogami, Wataru / Hirata, Michinari / Ueyama, Azumi / Yoshida, Tetsuya / Yoshikawa, Mai / Shinonome, Satomi / Yoshida, Hiroshi / Haruna, Miya / Miwa, Hiroto / Chatani, Natsumi / Ohkura, Naganari / Wada, Hisashi / Tanaka, Hidekazu

Molecular cancer therapeutics

2023 Volume 22, Issue 9, Page(s) 1063–1072

Abstract: Although regulatory T cells (Treg) are inhibitory immune cells that are essential for maintaining immune homeostasis, Tregs that infiltrate tumor tissue promote tumor growth by suppressing antitumor immunity. Selective reduction of tumor-infiltrating ... ...

Abstract	Although regulatory T cells (Treg) are inhibitory immune cells that are essential for maintaining immune homeostasis, Tregs that infiltrate tumor tissue promote tumor growth by suppressing antitumor immunity. Selective reduction of tumor-infiltrating Tregs is, therefore, expected to activate antitumor immunity without affecting immune homeostasis. We previously reported that selective Treg depletion targeted by a C-C motif chemokine receptor 8 (CCR8) resulted in induction of strong antitumor immunity without any obvious autoimmunity in mouse models. Thus, herein, we developed a novel humanized anti-CCR8 monoclonal antibody, S-531011, aimed as a cancer immunotherapy strategy for patients with cancer. S-531011 exclusively recognized human CCR8 among all chemokine receptors and showed potent antibody-dependent cell-mediated cytotoxicity activity toward CCR8+ cells and neutralization activity against CCR8-mediated signaling. We observed that S-531011 reduced tumor-infiltrating CCR8+ Tregs and induced potent antitumor activity in a tumor-bearing human-CCR8 knock-in mouse model. Moreover, combination therapy with S-531011 and anti-mouse programmed cell death 1 (PD-1) antibody strongly suppressed tumor growth compared with anti-PD-1 antibody alone with no observable adverse effects. S-531011 also depleted human tumor-infiltrating Tregs, but not Tregs derived from human peripheral blood mononuclear cells. These results suggest that S-531011 is a promising drug for inducing antitumor immunity without severe side effects in the clinical setting.
MeSH term(s)	Humans ; Receptors, Chemokine/metabolism ; T-Lymphocytes, Regulatory ; Neoplasms/drug therapy ; Immunity ; Lymphocytes, Tumor-Infiltrating
Chemical Substances	Receptors, Chemokine
Language	English
Publishing date	2023-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-22-0570
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Zs.A 5750: Show issues

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Article ; Online: T cell immunity in interstitial lung disease with non-small cell lung cancer patients.

Isono, Tomomi / Iwahori, Kota / Yanagawa, Masahiro / Yamamoto, Yoko / Tone, Mari / Haruna, Miya / Hirata, Michinari / Fukui, Eriko / Kimura, Toru / Kanou, Takashi / Ose, Naoko / Funaki, Soichiro / Takeda, Yoshito / Morii, Eiichi / Kumanogoh, Atsushi / Shintani, Yasushi / Wada, Hisashi

Lung cancer (Amsterdam, Netherlands)

2023 Volume 182, Page(s) 107278

Abstract: Objectives: Limited treatment options are available for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). The rationale for immunotherapy and its adverse events for NSCLC with ILD remains unclear. In this study, we ... ...

Abstract	Objectives: Limited treatment options are available for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). The rationale for immunotherapy and its adverse events for NSCLC with ILD remains unclear. In this study, we examined T cell profiles and functions in the lung tissues of NSCLC patients with or without ILD to provide evidence for the potential mechanism of immune checkpoint inhibitor (ICI)-related pneumonitis in NSCLC patients with ILD. Material and methods: We investigated T cell immunity in the lung tissues of NSCLC patients with ILD to support the application of immunotherapy for these patients. We analyzed T cell profiles and functions in surgically resected lung tissues from NSCLC patients with and without ILD. The T cell profiles of infiltrating cells in lung tissues were analyzed by flow cytometry. T cell functions were measured based on cytokine production by T cells stimulated with phorbol 12-myristate 13-acetate and ionomycin. Results: The percentages of CD4 Conclusion: In NSCLC patients with ILD stable for surgery, T cells were active participants and balanced in part by Treg cells in lung tissues, suggesting the potential development of ICI-related pneumonitis in NSCLC patients with ILD.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/therapy ; Lung Neoplasms/therapy ; CD8-Positive T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Lung Diseases, Interstitial ; Pneumonia ; Retrospective Studies
Chemical Substances	Tumor Necrosis Factor-alpha
Language	English
Publishing date	2023-06-09
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2023.107278
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The impact of CCR8+ regulatory T cells on cytotoxic T cell function in human lung cancer.

Haruna, Miya / Ueyama, Azumi / Yamamoto, Yoko / Hirata, Michinari / Goto, Kumiko / Yoshida, Hiroshi / Higuchi, Naoko / Yoshida, Tetsuya / Kidani, Yujiro / Nakamura, Yamami / Nagira, Morio / Kawashima, Atsunari / Iwahori, Kota / Shintani, Yasushi / Ohkura, Naganari / Wada, Hisashi

Scientific reports

2022 Volume 12, Issue 1, Page(s) 5377

Abstract: Regulatory T cells (Tregs) suppress the host immune response and maintain immune homeostasis. Tregs also promote cancer progression and are involved in resistance to immune checkpoint inhibitor treatments. Recent studies identified selective CCR8 ... ...

Abstract	Regulatory T cells (Tregs) suppress the host immune response and maintain immune homeostasis. Tregs also promote cancer progression and are involved in resistance to immune checkpoint inhibitor treatments. Recent studies identified selective CCR8 expression on tumor-infiltrating Tregs; CCR8+ Tregs have been indicated as a possible new target of cancer immunotherapy. Here, we investigated the features of CCR8+ Tregs in lung cancer patients. CCR8+ Tregs were highly activated and infiltration of CCR8+ Tregs in tumors was associated with poor prognosis in lung cancer patients. We also investigated their immune suppressive function, especially the influence on cytotoxic T lymphocyte cell function. The Cancer Genome Atlas analysis revealed that CD8 T cell activities were suppressed in high CCR8-expressing tumors. Additionally, depletion of CCR8+ cells enhanced CD8 T cell function in an ex vivo culture of lung tumor-infiltrating cells. Moreover, CCR8+ Tregs, but not CCR8- Tregs, induced from human PBMCs markedly suppressed CD8 T cell cytotoxicity. Finally, we demonstrated the therapeutic effect of targeting CCR8 in a murine model of lung cancer. These findings reveal the significance of CCR8+ Tregs for immunosuppression in lung cancer, especially via cytotoxic T lymphocyte cell suppression, and suggest the potential value of CCR8-targeted therapy for cancer treatment.
MeSH term(s)	Animals ; Humans ; Immune Tolerance ; Immunotherapy ; Lung Neoplasms/pathology ; Mice ; Receptors, CCR8/metabolism ; T-Lymphocytes, Cytotoxic ; T-Lymphocytes, Regulatory
Chemical Substances	CCR8 protein, human ; Ccr8 protein, mouse ; Receptors, CCR8
Language	English
Publishing date	2022-03-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-09458-5
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Article ; Online: Tumor-infiltrating ICOS

Kajikawa, Hitomi / Hirata, Michinari / Haruna, Miya / Ueyama, Azumi / Hirose, Katsutoshi / Kawashima, Atsunari / Iwahori, Kota / Matsunaga, Kazuhide / Toyosawa, Satoru / Uzawa, Narikazu / Wada, Hisashi

Anticancer research

2022 Volume 42, Issue 5, Page(s) 2383–2393

Abstract: Background: Tumor immunity in the tumor microenvironment is activated in patients with feasible clinical responses to immune checkpoint inhibitors. The immunological profile of tumor-infiltrating lymphocytes (TILs) obtained from patients with oral ... ...

Abstract	Background: Tumor immunity in the tumor microenvironment is activated in patients with feasible clinical responses to immune checkpoint inhibitors. The immunological profile of tumor-infiltrating lymphocytes (TILs) obtained from patients with oral squamous cell carcinoma (OSCC) was examined in relation to their prognosis. Materials and methods: Surface antigens, including immune checkpoint molecules, on TILs from 31 patients with primary OSCC were analyzed by flow cytometry. The activation status of TILs was examined through a heatmap analysis and unsupervised clustering classified patients into groups with activated or inactivated TILs. A supervised machine-learning algorithm for single-cell analyses in relation to prognosis was run using the Cluster Identification, Characterization, and Regression (CITRUS) program. Results: None of surface antigens were related to prognosis. The CITRUS program revealed a relationship between CD45RA Conclusion: CD25
MeSH term(s)	Carcinoma, Squamous Cell ; Head and Neck Neoplasms ; Humans ; Immune Checkpoint Inhibitors ; Inducible T-Cell Co-Stimulator Protein/metabolism ; Mouth Neoplasms/pathology ; Prognosis ; Squamous Cell Carcinoma of Head and Neck ; T-Lymphocytes, Regulatory ; Tumor Microenvironment
Chemical Substances	ICOS protein, human ; Immune Checkpoint Inhibitors ; Inducible T-Cell Co-Stimulator Protein
Language	English
Publishing date	2022-04-27
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15717
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Zs.A 1642: Show issues

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Article ; Online: Distribution analysis of epertinib in brain metastasis of HER2-positive breast cancer by imaging mass spectrometry and prospect for antitumor activity.

Tanaka, Yukari / Hirata, Michinari / Shinonome, Satomi / Torii, Mikinori / Nezasa, Ken-Ichi / Tanaka, Hidekazu

Scientific reports

2018 Volume 8, Issue 1, Page(s) 343

Abstract: Epertinib (S-222611) is a potent, reversible, and selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), human EGFR2 (HER2), and human EGFR4. We developed experimental brain metastasis models by intraventricular injection ( ... ...

Abstract	Epertinib (S-222611) is a potent, reversible, and selective tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), human EGFR2 (HER2), and human EGFR4. We developed experimental brain metastasis models by intraventricular injection (intraventricular injection mouse model; IVM) of HER2-positive breast cancer (MDA-MB-361-luc-BR2/BR3) or T790M-EGFR-positive lung cancer (NCI-H1975-luc) cells. After a single oral administration, epertinib and lapatinib concentrations in brain metastatic regions were analyzed by quantitative imaging mass spectrometry. In the NCI-H1975 lung cancer IVM, the concentration of epertinib in brain metastasis was comparable to that of lapatinib. However, in the MDA-MB-361 breast cancer IVM, the concentration of epertinib in brain metastasis was >10 times higher than that of lapatinib. Furthermore, the epertinib tumor-to-normal brain ratio was ~4 times higher than that of lapatinib. Blood-tumor barrier (BTB) permeability was assessed in each brain metastatic region. In the lung cancer model, fluorescently labeled dextran was more highly detected in brain metastatic regions than in brain parenchyma. However, in breast cancer models, dextran fluorescence intensity in brain metastatic regions and brain parenchyma were comparable, suggesting that the BTB remained largely intact. Epertinib would be promised as a therapeutic agent for HER2-positive breast cancer with brain metastasis.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacokinetics ; Brain Neoplasms/drug therapy ; Brain Neoplasms/mortality ; Brain Neoplasms/secondary ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Drug Monitoring ; Female ; Humans ; Mass Spectrometry ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacokinetics ; Quinazolines/pharmacokinetics ; Receptor, ErbB-2/metabolism ; Tissue Distribution ; Treatment Outcome ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Quinazolines ; lapatinib (0VUA21238F) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2018-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-017-18702-2
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Article ; Online: The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer.

Nose, Yohei / Saito, Takuro / Yamamoto, Kei / Yamashita, Kotaro / Tanaka, Koji / Yamamoto, Kazuyoshi / Makino, Tomoki / Takahashi, Tsuyoshi / Kawashima, Atsunari / Haruna, Miya / Hirata, Michinari / Ueyama, Azumi / Iwahori, Kota / Satoh, Taroh / Kurokawa, Yukinori / Eguchi, Hidetoshi / Doki, Yuichiro / Wada, Hisashi

Cancer immunology, immunotherapy : CII

2022 Volume 72, Issue 1, Page(s) 169–181

Abstract: Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell ... ...

Abstract	Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell death protein 1 (PD-1) antibody (nivolumab) in patients with gastric cancer. Methods: We collected peripheral blood samples from gastric cancer patients (n = 29) before and after treatment with nivolumab and investigated the relationship between the frequency of surface or intracellular markers among nivolumab-binding PD-1 Results: Patients with a high frequency of CD103 among PD-1 Conclusions: A high frequency of CD103 among PD-1
MeSH term(s)	Humans ; Stomach Neoplasms/pathology ; Nivolumab/therapeutic use ; Nivolumab/pharmacology ; CD8-Positive T-Lymphocytes ; Biomarkers/metabolism ; Progression-Free Survival
Chemical Substances	Nivolumab (31YO63LBSN) ; Biomarkers
Language	English
Publishing date	2022-07-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	195342-4
ISSN	1432-0851 ; 0340-7004
ISSN (online)	1432-0851
ISSN	0340-7004
DOI	10.1007/s00262-022-03240-2
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Zs.A 1237: Show issues

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Article ; Online: Immunotherapeutic potential of CD4 and CD8 single-positive T cells in thymic epithelial tumors.

Yamamoto, Yoko / Iwahori, Kota / Funaki, Soichiro / Matsumoto, Mitsunobu / Hirata, Michinari / Yoshida, Tetsuya / Kanzaki, Ryu / Kanou, Takashi / Ose, Naoko / Minami, Masato / Sato, Eiichi / Kumanogoh, Atsushi / Shintani, Yasushi / Okumura, Meinoshin / Wada, Hisashi

Scientific reports

2020 Volume 10, Issue 1, Page(s) 4064

Abstract: Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy ... ...

Abstract	Indications for current immune checkpoint inhibitors are expanding and now include thymic epithelial tumors (TETs). Although clinical trials on immune checkpoint inhibitors for TETs are ongoing, a rationale has not yet been established for immunotherapy for TETs. Therefore, we herein performed phenotypic and functional analyses of T cells in surgically resected TET tissues with a focus on the anti-tumor properties of T cells to TETs as a step towards establishing a rationale for immunotherapy for TETs. We examined T-cell profiles in surgically resected TET tissues, particularly CD4 and CD8 single-positive T cells, using flow cytometry. In the functional analysis of T cells in TETs, we investigated not only cytokine production by T cells, but also their cytotoxicity using bispecific T-cell engager technology. The cluster analysis of T-cell profiles based on flow cytometric data revealed that type B3 thymoma and thymic carcinoma (B3/C) belonged to the hot cluster characterized by a high proportion of Tim-3+ and CD103+ in CD4 and CD8 single-positive T cells. Enhancements in cytokine production and the cytotoxicity of T cells by the anti-PD-1 antibody were significantly greater in B3/C. These results indicate the potential of immunotherapy for patients with B3/C.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Female ; Humans ; Immunity, Cellular ; Immunotherapy ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial/immunology ; Neoplasms, Glandular and Epithelial/pathology ; Neoplasms, Glandular and Epithelial/therapy ; Thymus Neoplasms/immunology ; Thymus Neoplasms/pathology ; Thymus Neoplasms/therapy
Language	English
Publishing date	2020-03-04
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-61053-8
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Article ; Online: Docetaxel Upregulates HMGB1 Levels in Non-small Cell Lung Cancer.

Haruna, Miya / Hirata, Michinari / Iwahori, Kota / Kanazawa, Takayuki / Yamamoto, Yoko / Goto, Kumiko / Kawashima, Atsunari / Morimoto-Okazawa, Akiko / Funaki, Soichiro / Shintani, Yasushi / Kumanogoh, Atsushi / Wada, Hisashi

Biological & pharmaceutical bulletin

2020 Volume 43, Issue 3, Page(s) 399–403

Abstract: Immune checkpoint inhibitors (ICIs) exert beneficial effects in non-small cell lung cancer (NSCLC) patients. However, ICIs are only advantageous for a limited population of NSCLC patients. Therefore to enhance their effects, combination therapies with ... ...

Abstract	Immune checkpoint inhibitors (ICIs) exert beneficial effects in non-small cell lung cancer (NSCLC) patients. However, ICIs are only advantageous for a limited population of NSCLC patients. Therefore to enhance their effects, combination therapies with ICIs have been developed. To identify preferable chemotherapy to combine with ICIs against lung cancer, we examined immunological effects of docetaxel compared with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We found no difference in peripheral lymphocyte counts and ratio of their subpopulations in lung cancer patients before and after both treatments. On the other hand, plasma levels of high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) protein, showed significant increase after docetaxel treatment. Furthermore, we investigated effects of HMGB1 on tumor-infiltrating immune cells obtained from surgically resected tumor tissue from NSCLC patients. When the tumor infiltrating cells were stimulated with HMGB1, CD11c
MeSH term(s)	A549 Cells ; Antineoplastic Agents ; CD11 Antigens/metabolism ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Cell Line, Tumor ; Chemokines/metabolism ; Combined Modality Therapy ; Cytokines/metabolism ; Docetaxel/pharmacology ; Epidermal Growth Factor/antagonists & inhibitors ; ErbB Receptors/antagonists & inhibitors ; Female ; HMGB1 Protein/blood ; HMGB1 Protein/metabolism ; Humans ; Integrin alpha Chains/metabolism ; Male ; Mutation ; Protein Kinase Inhibitors/pharmacology ; Protein-Tyrosine Kinases/antagonists & inhibitors ; Transcriptional Activation/drug effects
Chemical Substances	Antineoplastic Agents ; CD11 Antigens ; Chemokines ; Cytokines ; HMGB1 Protein ; HMGB1 protein, human ; ITGAD protein, human ; Integrin alpha Chains ; Protein Kinase Inhibitors ; Docetaxel (15H5577CQD) ; Epidermal Growth Factor (62229-50-9) ; ErbB Receptors (EC 2.7.10.1) ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2020-02-28
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b19-00702
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