Eribulin mesylate exerts antitumor effects via CD103
Eribulin mesylate (ERB) is a synthetic analog of halichondrin B, inhibiting tumor cell growth by disrupting microtubule function. Recently, anticancer drugs have been shown to not only act directly on tumor cells but also to exert antitumor effects by modifying the tumor environment. Although ERB ha...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2218782 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850238259828883456 |
|---|---|
| author | Kazumasa Oya Yoshiyuki Nakamura Rei Watanabe Ryota Tanaka Yuki Ichimura Noriko Kubota Yutaka Matsumura Hideaki Tahara Naoko Okiyama Manabu Fujimoto Toshifumi Nomura Yasuhiro Fujisawa |
| author_facet | Kazumasa Oya Yoshiyuki Nakamura Rei Watanabe Ryota Tanaka Yuki Ichimura Noriko Kubota Yutaka Matsumura Hideaki Tahara Naoko Okiyama Manabu Fujimoto Toshifumi Nomura Yasuhiro Fujisawa |
| author_sort | Kazumasa Oya |
| collection | DOAJ |
| description | Eribulin mesylate (ERB) is a synthetic analog of halichondrin B, inhibiting tumor cell growth by disrupting microtubule function. Recently, anticancer drugs have been shown to not only act directly on tumor cells but also to exert antitumor effects by modifying the tumor environment. Although ERB has also been speculated to modify the tumor microenvironment including the immune response to tumors, the precise mechanism remains unclear. In our study, ERB suppressed the tumor growth of MC38 colon cancer in wildtype mice, whereas ERB failed to inhibit the tumor growth in Rag1-deficient mice which lack both B and T cells. Moreover, depletion of either CD4+ or CD8+ T cells abrogated the antitumor effect of ERB, indicating that both CD4+ and CD8+ T cells play an important role in ERB-induced antitumor effects. Furthermore, ERB treatment increased the number of tumor infiltrating lymphocytes (TILs) as well as the expression of activation markers (CD38 and CD69), immune checkpoint molecules (LAG3, TIGIT and Tim3) and cytotoxic molecules (granzyme B and perforin) in TILs. ERB upregulated E-cadherin expression in MC38. CD103 is a ligand of E-cadherin and induces T-cell activation. ERB increased the proportion of CD103+ cells in both CD4+ and CD8+ TILs. The ERB-induced antitumor effect with the increased TIL number and the increased expression of activation markers, inhibitory checkpoint molecules and cytotoxic molecules in TILs was abrogated in CD103-deficient mice. Collectively, these results suggest that ERB exerts antitumor effects by upregulation of E-cadherin expression in tumor cells and subsequent activation of CD103+ TILs. |
| format | Article |
| id | doaj-art-e8d35e9ee38e423c8bdae4bb3ecb9b00 |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-e8d35e9ee38e423c8bdae4bb3ecb9b002025-08-20T02:01:30ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2218782Eribulin mesylate exerts antitumor effects via CD103Kazumasa Oya0Yoshiyuki Nakamura1Rei Watanabe2Ryota Tanaka3Yuki Ichimura4Noriko Kubota5Yutaka Matsumura6Hideaki Tahara7Naoko Okiyama8Manabu Fujimoto9Toshifumi Nomura10Yasuhiro Fujisawa11The Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanThe Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanThe Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka, JapanThe Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanThe Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanThe Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanThe Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka, JapanProject Division of Cancer Biomolecular Therapy, Institute of Medical Science, The University of Tokyo, Tokyo, JapanDepartment of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, JapanThe Department of Dermatology, Graduate School of Medicine, Osaka University, Osaka, JapanThe Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanThe Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanEribulin mesylate (ERB) is a synthetic analog of halichondrin B, inhibiting tumor cell growth by disrupting microtubule function. Recently, anticancer drugs have been shown to not only act directly on tumor cells but also to exert antitumor effects by modifying the tumor environment. Although ERB has also been speculated to modify the tumor microenvironment including the immune response to tumors, the precise mechanism remains unclear. In our study, ERB suppressed the tumor growth of MC38 colon cancer in wildtype mice, whereas ERB failed to inhibit the tumor growth in Rag1-deficient mice which lack both B and T cells. Moreover, depletion of either CD4+ or CD8+ T cells abrogated the antitumor effect of ERB, indicating that both CD4+ and CD8+ T cells play an important role in ERB-induced antitumor effects. Furthermore, ERB treatment increased the number of tumor infiltrating lymphocytes (TILs) as well as the expression of activation markers (CD38 and CD69), immune checkpoint molecules (LAG3, TIGIT and Tim3) and cytotoxic molecules (granzyme B and perforin) in TILs. ERB upregulated E-cadherin expression in MC38. CD103 is a ligand of E-cadherin and induces T-cell activation. ERB increased the proportion of CD103+ cells in both CD4+ and CD8+ TILs. The ERB-induced antitumor effect with the increased TIL number and the increased expression of activation markers, inhibitory checkpoint molecules and cytotoxic molecules in TILs was abrogated in CD103-deficient mice. Collectively, these results suggest that ERB exerts antitumor effects by upregulation of E-cadherin expression in tumor cells and subsequent activation of CD103+ TILs.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2218782antitumor effectCD103eribulin mesylateimmune checkpointresident memory T cells |
| spellingShingle | Kazumasa Oya Yoshiyuki Nakamura Rei Watanabe Ryota Tanaka Yuki Ichimura Noriko Kubota Yutaka Matsumura Hideaki Tahara Naoko Okiyama Manabu Fujimoto Toshifumi Nomura Yasuhiro Fujisawa Eribulin mesylate exerts antitumor effects via CD103 OncoImmunology antitumor effect CD103 eribulin mesylate immune checkpoint resident memory T cells |
| title | Eribulin mesylate exerts antitumor effects via CD103 |
| title_full | Eribulin mesylate exerts antitumor effects via CD103 |
| title_fullStr | Eribulin mesylate exerts antitumor effects via CD103 |
| title_full_unstemmed | Eribulin mesylate exerts antitumor effects via CD103 |
| title_short | Eribulin mesylate exerts antitumor effects via CD103 |
| title_sort | eribulin mesylate exerts antitumor effects via cd103 |
| topic | antitumor effect CD103 eribulin mesylate immune checkpoint resident memory T cells |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2218782 |
| work_keys_str_mv | AT kazumasaoya eribulinmesylateexertsantitumoreffectsviacd103 AT yoshiyukinakamura eribulinmesylateexertsantitumoreffectsviacd103 AT reiwatanabe eribulinmesylateexertsantitumoreffectsviacd103 AT ryotatanaka eribulinmesylateexertsantitumoreffectsviacd103 AT yukiichimura eribulinmesylateexertsantitumoreffectsviacd103 AT norikokubota eribulinmesylateexertsantitumoreffectsviacd103 AT yutakamatsumura eribulinmesylateexertsantitumoreffectsviacd103 AT hideakitahara eribulinmesylateexertsantitumoreffectsviacd103 AT naokookiyama eribulinmesylateexertsantitumoreffectsviacd103 AT manabufujimoto eribulinmesylateexertsantitumoreffectsviacd103 AT toshifuminomura eribulinmesylateexertsantitumoreffectsviacd103 AT yasuhirofujisawa eribulinmesylateexertsantitumoreffectsviacd103 |