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6. Immune microenvironment, homologous recombination deficiency, and therapeutic response to neoadjuvant chemotherapy in triple-negative breast cancer: Japan Breast Cancer Research Group (JBCRG)22 TR

Author

Ueno, Takayuki, Kitano, Shigehisa, Masuda, Norikazu, Ikarashi, Daiki, Yamashita, Makiko, Chiba, Tomohiro, Kadoya, Takayuki, Bando, Hiroko, Yamanaka, Takashi, Ohtani, Shoichiro, Nagai, Shigenori, Nakayama, Takahiro, Takahashi, Masato, Saji, Shigehira, Aogi, Kenjiro, Velaga, Ravi, Kawaguchi, Kosuke, Morita, Satoshi, Haga, Hironori, Ohno, Shinji, and Toi, Masakazu

Published
2022
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8. Molecular subtypes of lung adenocarcinoma present distinct immune tumor microenvironments

Author

Fukuda, Hironori, primary, Arai, Kosuke, additional, Mizuno, Hideaki, additional, Nishito, Yukari, additional, Motoi, Noriko, additional, Arai, Yasuhito, additional, Hiraoka, Nobuyoshi, additional, Shibata, Tatsuhiro, additional, Sonobe, Yukiko, additional, Kayukawa, Yoko, additional, Hashimoto, Eri, additional, Takahashi, Mina, additional, Fujii, Etsuko, additional, Maruyama, Toru, additional, Kuwabara, Kenta, additional, Nishizawa, Takashi, additional, Mizoguchi, Yukihiro, additional, Yoshida, Yukihiro, additional, Watanabe, Shun‐ichi, additional, Yamashita, Makiko, additional, Kitano, Shigehisa, additional, Sakamoto, Hiromi, additional, Nagata, Yuki, additional, Mitsumori, Risa, additional, Ozaki, Kouichi, additional, Niida, Shumpei, additional, Kanai, Yae, additional, Hirayama, Akiyoshi, additional, Soga, Tomoyoshi, additional, Tsukada, Keisuke, additional, Yabuki, Nami, additional, Shimada, Mei, additional, Kitazawa, Takehisa, additional, Natori, Osamu, additional, Sawada, Noriaki, additional, Kato, Atsuhiko, additional, Yoshida, Teruhiko, additional, Yasuda, Kazuki, additional, Ochiai, Atsushi, additional, Tsunoda, Hiroyuki, additional, and Aoki, Kazunori, additional

Published
2024
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10. Interleukin‐4 induced 1‐mediated resistance to an immune checkpoint inhibitor through suppression of CD8+ T cell infiltration in melanoma.

Author

Hirose, Shiho, Mashima, Tetsuo, Yuan, Xunmei, Yamashita, Makiko, Kitano, Shigehisa, Torii, Shinichi, Migita, Toshiro, and Seimiya, Hiroyuki

Abstract

Cancer cells adopt multiple strategies to escape tumor surveillance by the host immune system and aberrant amino acid metabolism in the tumor microenvironment suppresses the immune system. Among the amino acid‐metabolizing enzymes is an L‐amino‐acid oxidase called interleukin‐4 induced 1 (IL4I1), which depletes essential amino acids in immune cells and is associated with a poor prognosis in various cancer types. Although IL4I1 is involved in immune metabolism abnormalities, its effect on the therapeutic efficacy of immune checkpoint inhibitors is unknown. In this study, we established murine melanoma cells overexpressing IL4I1 and investigated their effects on the intratumor immune microenvironment and the antitumor efficacy of anti‐programmed death‐ligand 1 (PD‐L1) antibodies (Abs) in a syngeneic mouse model. As a result, we found that IL4I1‐overexpressing B16‐F10‐derived tumors showed resistance to anti‐PD‐L1 Ab therapy. Transcriptome analysis revealed that immunosuppressive genes were globally upregulated in the IL4I1‐overexpressing tumors. Consistently, we showed that IL4I1‐overexpressing tumors exhibited an altered subset of lymphoid cells and particularly significant suppression of cytotoxic T cell infiltration compared to mock‐infected B16‐F10‐derived tumors. After treatment with anti‐PD‐L1 Abs, we also found a more prominent elevation of tumor‐associated macrophage (TAM) marker, CD68, in the IL4I1‐overexpressing tumors than in the mock tumors. Consistently, we confirmed an enhanced TAM infiltration in the IL4I1‐overexpressing tumors and a functional involvement of TAMs in the tumor growth. These observations indicate that IL4I1 reprograms the tumor microenvironment into an immunosuppressive state and thereby confers resistance to anti‐PD‐L1 Abs. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Investigating the immunological function of alpha-2-glycoprotein 1, zinc-binding in regulating tumor response in the breast cancer microenvironment

Author

Hanamura, Toru, primary, Yokoyama, Kozue, additional, Kitano, Shigehisa, additional, Kagamu, Hiroshi, additional, Yamashita, Makiko, additional, Terao, Mayako, additional, Okamura, Takuho, additional, Kumaki, Nobue, additional, Hozumi, Katsuto, additional, Iwamoto, Takayuki, additional, Honda, Chikako, additional, Kurozumi, Sasagu, additional, Richer, Jennifer K, additional, and Niikura, Naoki, additional

Published
2023
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12. FIGURE 5 from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

Author

Aoki, Kazunori, primary, Nishito, Yukari, primary, Motoi, Noriko, primary, Arai, Yasuhito, primary, Hiraoka, Nobuyoshi, primary, Shibata, Tatsuhiro, primary, Sonobe, Yukiko, primary, Kayukawa, Yoko, primary, Hashimoto, Eri, primary, Takahashi, Mina, primary, Fujii, Etsuko, primary, Nishizawa, Takashi, primary, Fukuda, Hironori, primary, Ohashi, Kana, primary, Arai, Kosuke, primary, Mizoguchi, Yukihiro, primary, Yoshida, Yukihiro, primary, Watanabe, Shun-ichi, primary, Yamashita, Makiko, primary, Kitano, Shigehisa, primary, Sakamoto, Hiromi, primary, Nagata, Yuki, primary, Mitsumori, Risa, primary, Ozaki, Kouichi, primary, Niida, Shumpei, primary, Kanai, Yae, primary, Hirayama, Akiyoshi, primary, Soga, Tomoyoshi, primary, Maruyama, Toru, primary, Tsukada, Keisuke, primary, Yabuki, Nami, primary, Shimada, Mei, primary, Kitazawa, Takehisa, primary, Natori, Osamu, primary, Sawada, Noriaki, primary, Kato, Atsuhiko, primary, Yoshida, Teruhiko, primary, Yasuda, Kazuki, primary, Mizuno, Hideaki, primary, Tsunoda, Hiroyuki, primary, and Ochiai, Atsushi, primary

Published
2023
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13. Table S3 from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

Author

Aoki, Kazunori, primary, Nishito, Yukari, primary, Motoi, Noriko, primary, Arai, Yasuhito, primary, Hiraoka, Nobuyoshi, primary, Shibata, Tatsuhiro, primary, Sonobe, Yukiko, primary, Kayukawa, Yoko, primary, Hashimoto, Eri, primary, Takahashi, Mina, primary, Fujii, Etsuko, primary, Nishizawa, Takashi, primary, Fukuda, Hironori, primary, Ohashi, Kana, primary, Arai, Kosuke, primary, Mizoguchi, Yukihiro, primary, Yoshida, Yukihiro, primary, Watanabe, Shun-ichi, primary, Yamashita, Makiko, primary, Kitano, Shigehisa, primary, Sakamoto, Hiromi, primary, Nagata, Yuki, primary, Mitsumori, Risa, primary, Ozaki, Kouichi, primary, Niida, Shumpei, primary, Kanai, Yae, primary, Hirayama, Akiyoshi, primary, Soga, Tomoyoshi, primary, Maruyama, Toru, primary, Tsukada, Keisuke, primary, Yabuki, Nami, primary, Shimada, Mei, primary, Kitazawa, Takehisa, primary, Natori, Osamu, primary, Sawada, Noriaki, primary, Kato, Atsuhiko, primary, Yoshida, Teruhiko, primary, Yasuda, Kazuki, primary, Mizuno, Hideaki, primary, Tsunoda, Hiroyuki, primary, and Ochiai, Atsushi, primary

Published
2023
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14. FIGURE 3 from Tumor-infiltrating Leukocyte Profiling Defines Three Immune Subtypes of NSCLC with Distinct Signaling Pathways and Genetic Alterations

Author

Aoki, Kazunori, primary, Nishito, Yukari, primary, Motoi, Noriko, primary, Arai, Yasuhito, primary, Hiraoka, Nobuyoshi, primary, Shibata, Tatsuhiro, primary, Sonobe, Yukiko, primary, Kayukawa, Yoko, primary, Hashimoto, Eri, primary, Takahashi, Mina, primary, Fujii, Etsuko, primary, Nishizawa, Takashi, primary, Fukuda, Hironori, primary, Ohashi, Kana, primary, Arai, Kosuke, primary, Mizoguchi, Yukihiro, primary, Yoshida, Yukihiro, primary, Watanabe, Shun-ichi, primary, Yamashita, Makiko, primary, Kitano, Shigehisa, primary, Sakamoto, Hiromi, primary, Nagata, Yuki, primary, Mitsumori, Risa, primary, Ozaki, Kouichi, primary, Niida, Shumpei, primary, Kanai, Yae, primary, Hirayama, Akiyoshi, primary, Soga, Tomoyoshi, primary, Maruyama, Toru, primary, Tsukada, Keisuke, primary, Yabuki, Nami, primary, Shimada, Mei, primary, Kitazawa, Takehisa, primary, Natori, Osamu, primary, Sawada, Noriaki, primary, Kato, Atsuhiko, primary, Yoshida, Teruhiko, primary, Yasuda, Kazuki, primary, Mizuno, Hideaki, primary, Tsunoda, Hiroyuki, primary, and Ochiai, Atsushi, primary

Published
2023
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15. Tumor-infiltrating leukocyte profiling defines three immune subtypes of NSCLC with distinct signaling pathways and genetic alterations

Author

Aoki, Kazunori, primary, Nishito, Yukari, additional, Motoi, Noriko, additional, Arai, Yasuhito, additional, Hiraoka, Nobuyoshi, additional, Shibata, Tatsuhiro, additional, Sonobe, Yukiko, additional, Kayukawa, Yoko, additional, Hashimoto, Eri, additional, Takahashi, Mina, additional, Fujii, Etsuko, additional, Nishizawa, Takashi, additional, Fukuda, Hironori, additional, Ohashi, Kana, additional, Arai, Kosuke, additional, Mizoguchi, Yukihiro, additional, Yoshida, Yukihiro, additional, Watanabe, Shun-ichi, additional, Yamashita, Makiko, additional, Kitano, Shigehisa, additional, Sakamoto, Hiromi, additional, Nagata, Yuki, additional, Mitsumori, Risa, additional, Ozaki, Kouichi, additional, Niida, Shumpei, additional, Kanai, Yae, additional, Hirayama, Akiyoshi, additional, Soga, Tomoyoshi, additional, Maruyama, Toru, additional, Tsukada, Keisuke, additional, Yabuki, Nami, additional, Shimada, Mei, additional, Kitazawa, Takehisa, additional, Natori, Osamu, additional, Sawada, Noriaki, additional, Kato, Atsuhiko, additional, Yoshida, Teruhiko, additional, Yasuda, Kazuki, additional, Mizuno, Hideaki, additional, Tsunoda, Hiroyuki, additional, and Ochiai, Atsushi, additional

Published
2023
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17. Supplementary Figures 1-7, Supplementary Tables 1-8, 12 from Transient Depletion of CD4+ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer

Author

Aoki, Hiroyasu, primary, Ueha, Satoshi, primary, Shichino, Shigeyuki, primary, Ogiwara, Haru, primary, Shitara, Kohei, primary, Shimomura, Manami, primary, Suzuki, Toshihiro, primary, Nakatsura, Tetsuya, primary, Yamashita, Makiko, primary, Kitano, Shigehisa, primary, Kuroda, Sakiko, primary, Wakabayashi, Masashi, primary, Kurachi, Makoto, primary, Ito, Satoru, primary, Doi, Toshihiko, primary, and Matsushima, Kouji, primary

Published
2023
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18. Table S11 from Transient Depletion of CD4+ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer

Author

Aoki, Hiroyasu, primary, Ueha, Satoshi, primary, Shichino, Shigeyuki, primary, Ogiwara, Haru, primary, Shitara, Kohei, primary, Shimomura, Manami, primary, Suzuki, Toshihiro, primary, Nakatsura, Tetsuya, primary, Yamashita, Makiko, primary, Kitano, Shigehisa, primary, Kuroda, Sakiko, primary, Wakabayashi, Masashi, primary, Kurachi, Makoto, primary, Ito, Satoru, primary, Doi, Toshihiko, primary, and Matsushima, Kouji, primary

Published
2023
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19. Data from Transient Depletion of CD4+ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer

Author

Aoki, Hiroyasu, primary, Ueha, Satoshi, primary, Shichino, Shigeyuki, primary, Ogiwara, Haru, primary, Shitara, Kohei, primary, Shimomura, Manami, primary, Suzuki, Toshihiro, primary, Nakatsura, Tetsuya, primary, Yamashita, Makiko, primary, Kitano, Shigehisa, primary, Kuroda, Sakiko, primary, Wakabayashi, Masashi, primary, Kurachi, Makoto, primary, Ito, Satoru, primary, Doi, Toshihiko, primary, and Matsushima, Kouji, primary

Published
2023
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20. Abstract P5-02-42: Soluble CD163 may be a predictive biomarker of the efficacy of nivolumab plus chemotherapy in patients with HER2-negative metastatic breast cancer (WJOG9917BTR)

Author

Mukohara, Toru, primary, Ozaki, Yukinori, additional, Kitano, Shigehisa, additional, Yamashita, Makiko, additional, Ikarashi, Daiki, additional, Tsurutani, Junji, additional, Iwasa, Tsutomu, additional, Takahashi, Masato, additional, Masuda, Norikazu, additional, Futamura, Manabu, additional, Minami, Hironobu, additional, Matsumoto, Koji, additional, Tanabe, Yuko, additional, Kawabata, Hidetaka, additional, Yoshimura, Kenichi, additional, and Takano, Toshimi, additional

Published
2023
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21. Abstract P2-20-16: Hormone receptor expression is associated with specific immunological profiles in the breast cancer microenvironment

Author

Hanamura, Toru, primary, Kitano, Shigehisa, additional, Kagamu, Hiroshi, additional, Yamashita, Makiko, additional, Terao, Mayako, additional, Okamura, Takuho, additional, Kumaki, Nobue, additional, Hozumi, Katsuto, additional, Iwamoto, Takayuki, additional, Honda, Chikako, additional, Kurozumi, Sasagu, additional, and Niikura, Naoki, additional

Published
2023
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22. First-in-human phase 1 study of IT1208, a defucosylated humanized anti-CD4 depleting antibody, in patients with advanced solid tumors

Author

Shitara, Kohei, Ueha, Satoshi, Shichino, Shigeyuki, Aoki, Hiroyasu, Ogiwara, Haru, Nakatsura, Tetsuya, Suzuki, Toshihiro, Shimomura, Manami, Yoshikawa, Toshiaki, Shoda, Kayoko, Kitano, Shigehisa, Yamashita, Makiko, Nakayama, Takayuki, Sato, Akihiro, Kuroda, Sakiko, Wakabayashi, Masashi, Nomura, Shogo, Yokochi, Shoji, Ito, Satoru, Matsushima, Kouji, and Doi, Toshihiko

Published
2019
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23. Comprehensive biomarker analysis from phase II study of nivolumab in patients with thymic carcinoma

Author

Katsuya, Yuki, primary, Kitano, Shigehisa, additional, Yamashita, Makiko, additional, Ouchi, Mayu, additional, Yagishita, Shigehiro, additional, Hamada, Akinobu, additional, Nakamura, Hiromi, additional, Hosoda, Fumie, additional, Shibata, Tatsuhiro, additional, Motoi, Noriko, additional, Nakayama, Takayuki, additional, Seto, Takashi, additional, Umemura, Shigeki, additional, Hosomi, Yukio, additional, Satouchi, Miyako, additional, Nishio, Makoto, additional, Kozuki, Toshiyuki, additional, Hida, Toyoaki, additional, Ohe, Yuichiro, additional, and Horinouchi, Hidehito, additional

Published
2023
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24. Additional file 1 of Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment

Author

Hanamura, Toru, Kitano, Shigehisa, Kagamu, Hiroshi, Yamashita, Makiko, Terao, Mayako, Okamura, Takuho, Kumaki, Nobue, Hozumi, Katsuto, Iwamoto, Takayuki, Honda, Chikako, Kurozumi, Sasagu, and Niikura, Naoki

Abstract

Additional file 1: Fig. S1. Association of typical biological processes with the expression of hormone receptors estimated using the gene expression profile of breast cancer. (a-f) Summary of results of GSEA performed on the METABRIC datasets is shown. Biological processes positively or inversely correlated with each gene expression are shown in the descending order of the absolute value of the normalized enrichment score (NSE) with absolute values of the log-transformed nominal p-values and FDR q-values. Thresholds of the nominal p-value and FDR q-value were set to < 0.05 and < 0.25, respectively, and the boundaries are shown in the graph by dashed lines. Fig. S2. Programmed death-ligand 1 (PD-L1) positive ratio in each immune cell fraction according to estrogen receptor (ER) status. (a-k) the percentage of PD-L1 positive cells in each immune cell fraction by ER status is shown. A summary of statistics value is shown at left side of figure. A summary of the recalculated statistics values excluding outliers is shown in the lower left of the figure. Fig. S3. Programmed death-ligand 1 PD-L1 positive ratio in each immune cell fraction according to progesterone receptor (PgR) status. (a-k) the percentage of PD-L1 positive cells in each immune cell fraction by PgR status is shown. A summary of statistics value is shown at left side of figure. A summary of the recalculated statistics values excluding outliers is shown in the lower left of the figure. Fig. S4. Programmed death-ligand 1 (PD-L1) positive ratio in each immune cell fraction according to androgen receptor (AR) status. (a-k) the percentage of PD-L1 positive cells in each immune cell fraction by AR status is shown. A summary of statistics value is shown at left side of figure. A summary of the recalculated statistics values excluding outliers is shown in the lower left of the figure. Fig. S5. Reanalysis of Figs. 2–4 using 1% cut-off point for ER and PgR. (a-d) Correlation of hTIL and hPD-L1 with protein expression of ER and PgR were reanalyzed using the cut-off points 1% for ER and PgR. (e, f) Association between ER / PgR status and subsets of tumor-infiltrating immune cells were reanalyzed using the cut-off points 1% for ER and PgR. (g, h) Recalculated statistics values excluding outliers are shown for ER and PgR status. Table S1. Clinical-pathological characteristics by ER status. Table S2. Clinical-pathological characteristics by PgR status. Table S3. Clinical-pathological characteristics by AR status.

Published
2023
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32. Efficient Acquisition of Antigen-Specific Human Monoclonal Antibody by Using Peripheral Blood Mononuclear Cells Immunized In Vitro : Efficient Cloning of Human Monoclonal Antibody Gene

Author

Matsumoto, Shinei, Yamashita, Makiko, Katakura, Yoshinori, Tomimatsu, Kosuke, Aiba, Yoshihiro, Teruya, Kiichiro, Shirahata, Sanetaka, Shirahata, Sanetaka, editor, Ikura, Koji, editor, Nagao, Masaya, editor, Ichikawa, Akira, editor, and Teruya, Kiichiro, editor

Published
2009
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34. Expression of hormone receptors is associated with specific immunological profiles of the breast cancer microenvironment

Author

Hanamura, Toru, primary, Kitano, Shigehisa, additional, Kagamu, Hiroshi, additional, Yamashita, Makiko, additional, Terao, Mayako, additional, Okamura, Takuho, additional, Kumaki, Nobue, additional, Hozumi, Katsuto, additional, Iwamoto, Takayuki, additional, Honda, Chikako, additional, Kurozumi, Sasagu, additional, and Niikura, Naoki, additional

Published
2022
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35. Telomere Shortening in Cancer Cells by Electrolyzed-Reduced Water

Author

Shirahata, Sanetaka, Murakami, En, Kusumoto, Ken-ichi, Yamashita, Makiko, Oda, Masaaki, Temya, Kiichiro, Kabayama, Shigeru, Otsubo, Kazumichi, Morisawa, Shinkatsu, Hayashi, Hidemitsu, Katakura, Yoshinori, Ikura, Kouji, editor, Nagao, Masaya, editor, Masuda, Seiji, editor, and Sasaki, Ryuzo, editor

Published
2002
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37. Abstract P4-04-09: Systematic analysis of immune cell composition revealed immunological profile of breast cancer microenvironment represented by histologically assessed tumor-infiltrating lymphocyte and PD-L1 expression

Author

Hanamura, Toru, primary, Kitano, Shigehisa, additional, Kagamu, Hiroshi, additional, Yamashita, Makiko, additional, Terao, Mayako, additional, Tsuda, Banri, additional, Okamura, Takuho, additional, Kumaki, Nobue, additional, Hozumi, Katsuto, additional, Harada, Naoki, additional, Iwamoto, Takaiki, additional, Honda, Chikako, additional, Kurozumi, Sasagu, additional, and Niikura, Naoki, additional

Published
2022
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39. Additional file 1 of Immune microenvironment, homologous recombination deficiency, and therapeutic response to neoadjuvant chemotherapy in triple-negative breast cancer: Japan Breast Cancer Research Group (JBCRG)22 TR

Author

Ueno, Takayuki, Kitano, Shigehisa, Masuda, Norikazu, Ikarashi, Daiki, Yamashita, Makiko, Chiba, Tomohiro, Kadoya, Takayuki, Bando, Hiroko, Yamanaka, Takashi, Ohtani, Shoichiro, Nagai, Shigenori, Nakayama, Takahiro, Takahashi, Masato, Saji, Shigehira, Aogi, Kenjiro, Velaga, Ravi, Kawaguchi, Kosuke, Morita, Satoshi, Haga, Hironori, Ohno, Shinji, and Toi, Masakazu

Abstract

Additional file 1: Figure S1. Image analysis. Representative image of immunofluorescence with the following markers: CD3 (blue), CD4 (yellow), CD8 (red), FoxP3 (pink), CD204 (green), and cytokeratin (brown) (A); tissue segmentation of the intratumoral (red) and stromal (green) areas (B); cell segmentation (C) and cell phenotyping (D) which merged with tissue segmentation (E): cancer cells (orange), CD4+ T cells (yellow), CD8+ T cells (red), CD204+ cells (green), other stromal cells (gray). Figure S2. Immune cell density according to pathological response in each treatment group: group A1 (A), group A2 (B), group B1 (C), group B2 (D). Figure S3. Immune phenotype and pCR. (A) Immune inflamed, high cell density in both cancer cell nests and stromal regions; immune excluded, low cell density in cancer cell nests and high cell density in stromal regions; immune desert, low cell densities in both cancer cell nests and stromal regions. (B) Immune phenotype for CD4+ T cells. (C) Immune phenotype for CD8+ T cells. (D) pCR rate according to immune phenotype for CD4+ T cells and CD8+ T cells.

Published
2022
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40. Immunological Profiles of The Breast Cancer Microenvironment Represented by Tumor-Infiltrating Lymphocytes and PD-L1 Expression

Author

Hanamura, Toru, primary, Kitano, Shigehisa, additional, Kagamu, Hiroshi, additional, Yamashita, Makiko, additional, Terao, Mayako, additional, Tsuda, Banri, additional, Okamura, Takuho, additional, Kumaki, Nobue, additional, Hozumi, Katsuto, additional, Harada, Naoki, additional, Iwamoto, Takayuki, additional, Honda, Chikako, additional, Kurozumi, Sasagu, additional, and Niikura, Naoki, additional

Published
2021
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41. Pretreatment tumour immune microenvironment predicts clinical response and prognosis of muscle-invasive bladder cancer in the neoadjuvant chemotherapy setting

Author

Ikarashi, Daiki, primary, Kitano, Shigehisa, additional, Tsuyukubo, Takashi, additional, Takenouchi, Kazumasa, additional, Nakayama, Takayuki, additional, Onagi, Hiroko, additional, Sakaguchi, Asumi, additional, Yamashita, Makiko, additional, Mizugaki, Hidenori, additional, Maekawa, Shigekatsu, additional, Kato, Renpei, additional, Kato, Yoichiro, additional, Sugai, Tamotsu, additional, Nakatsura, Tetsuya, additional, and Obara, Wataru, additional

Published
2021
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44. Immune cell composition and immunological profiles of the breast cancer microenvironment represented by histologically assessed tumor-infiltrating lymphocytes and PD-L1 expression: A systematic analysis

Author

Hanamura, Toru, primary, Kitano, Shigehisa, additional, Kagamu, Hiroshi, additional, Yamashita, Makiko, additional, Terao, Mayako, additional, Tsuda, Banri, additional, Okamura, Takuho, additional, Kumaki, Nobue, additional, Hozumi, Katsuto, additional, Harada, Naoki, additional, Iwamoto, Takayuki, additional, Honda, Chikako, additional, Kurozumi, Sasagu, additional, and Niikura, Naoki, additional

Published
2021
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48. Transient Depletion of CD4+ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer

Author

Aoki, Hiroyasu, primary, Ueha, Satoshi, additional, Shichino, Shigeyuki, additional, Ogiwara, Haru, additional, Shitara, Kohei, additional, Shimomura, Manami, additional, Suzuki, Toshihiro, additional, Nakatsura, Tetsuya, additional, Yamashita, Makiko, additional, Kitano, Shigehisa, additional, Kuroda, Sakiko, additional, Wakabayashi, Masashi, additional, Kurachi, Makoto, additional, Ito, Satoru, additional, Doi, Toshihiko, additional, and Matsushima, Kouji, additional

Published
2021
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49. Abstract PS4-14: Immunological analysis of the combination therapy of nivolumab, paclitaxel and bevacizumab in patients with HER2-negative MBC in NEWBEAT trial (WJOG9917BTR)

Author

Ozaki, Yukinori, primary, Kitano, Shigehisa, additional, Tsurutani, Junji, additional, Iwasa, Tsutomu, additional, Takahashi, Masato, additional, Mukohara, Toru, additional, Masuda, Norikazu, additional, Futamura, Manabu, additional, Minami, Hironobu, additional, Matsumoto, Koji, additional, Kawabata, Hidetaka, additional, Yamashita, Makiko, additional, Yoshimura, Kenichi, additional, and Takano, Toshimi, additional

Published
2021
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50. Depletion of cellular cholesterol enhances macrophage MAPK activation by chitin microparticles but not by heat-killed Mycobacterium bovis BCG

Author

Nishiyama, Akihito, Shinohara, Tsutomu, Pantuso, Traci, Tsuji, Shoutaro, Yamashita, Makiko, Shinohara, Shizuka, Myrvik, Quentin N., Henriksen, Ruth Ann, and Shibata, Yoshimi

Subjects
Chitin -- Properties, Cell physiology -- Research, Cholesterol -- Properties, Macrophages -- Properties, Biological sciences
Abstract

When macrophages phagocytose chitin (N-acetyl-D-glucosamine polymer) microparticles, mitogen-activated protein kinases (MAPK) are immediately activated, followed by the release of Th1 cytokines, but not IL-10. To determine whether phagocytosis and macrophage activation in response to chitin microparticles are dependent on membrane cholesterol, RAW264.7 macrophages were treated with methyl-[beta]-cytodextrin (MBCD) and stimulated with chitin. These results were compared with the corresponding effects of bacterial components including heat-killed (HK) Mycobacterium bovis bacillus Calmette-Guerin (BCG) and an oligodeoxynucleotide (ODN) of bacterial DNA (CpG-ODN). The MBCD treatment did not alter chitin binding or the phagocytosis of chitin particles 20 min after stimulation. At the same time, however, chitin-induced phosphorylation of cellular MAPK was accelerated and enhanced in an MBCD dose-dependent manner. The increased phosphorylation was also observed for chitin phagosome-associated p38 and ERK1/2. In contrast, CpG-ODN and HK-BCG induced activation of MAPK in MBCD-treated cells at levels comparable to, or only slightly more than, those of control cells. We also found that MBCD treatment enhanced the production of tumor necrosis factor-[alpha] (TNF-[alpha]) and the expression of cyclooxygenase-2 (COX-2) in response to chitin microparticles. In neither MBCD- nor saline-treated macrophages, did chitin particles induce detectable IL-10 mRNA synthesis. CpG-ODN induced TNF-[alpha] production, and COX-2 expression were less sensitive to MBCD treatment. Among the agonists studied, our results indicate that macrophage activation by chitin microparticles was most sensitive to cholesterol depletion, suggesting that membrane structures integrated by cholesterol are important for physiological regulation of chitin microparticle-induced cellular activation. N-acetyl-D-glucosamine polymer particles; phagosome formation; mitogen-activated protein kinase activation; Thl cytokines; interleukin-10; cyclooxygenase-2

Published
2008

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