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Inhibition of α4ß1 Integrin Activity by Small Tellurium Compounds Regulates PD-L1 Expression and Enhances Antitumor Effects.
Chaouat, Abigael; Kalechman, Yona; Hay, Ophir; Manoim, Julia E; Lantner, Tal; Niderberg, Eitan; Hauschner, Hagit; Sredni, Dvora Kenigsbuch; Cohen, Tal; Schlesinger, Agata; Nadler, Ronia; Barda-Saad, Mira; Noy, Elad; Albeck, Michael; Longo, Dan L; Sredni, Benjamin.
Afiliación
  • Chaouat A; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Kalechman Y; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Hay O; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Manoim JE; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Lantner T; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Niderberg E; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Hauschner H; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Sredni DK; Interdisciplinary Dept. Bar Ilan University, Ramat Gan, Israel.
  • Cohen T; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Schlesinger A; Hospital at Home, Clalit Health Services, Sharon-Shomron District. Department of Geriatrics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Nadler R; The Academic Center of Law and Science, Hod Hasharon, Israel.
  • Barda-Saad M; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Noy E; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
  • Albeck M; Dept. of Chemistry. Bar-Ilan University, Ramat Gan, Israel.
  • Longo DL; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  • Sredni B; C.A.I.R. Institute, The Safdiè AIDS and Immunology Research Center, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Int J Biol Sci ; 20(11): 4407-4423, 2024.
Article en En | MEDLINE | ID: mdl-39247817
ABSTRACT
Various cancer treatment approaches that inhibit the activity of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis, a key player in tumor immune evasion, have been developed. We show that the immunomodulatory small tellurium complexes AS101 (ammonium trichloro(dioxoethylene-o,o')tellurate) and SAS (octa-O-bis(R,R)-tartarate ditellurane) suppress PD-L1 expression in a variety of human and mouse malignant cells via the modulation of α4ß1 very late antigen-4 (VLA-4) integrin activity. Consequently, the expression of pAkt and its downstream effector pNFκB are inhibited. Additionally, SAS promotes the death of mouse malignant cells by activated syngeneic splenocytes or CD8+ T cells, preventing the development of chemoresistance in malignant cells. Moreover, AS101 and SAS may increase, at least in part, chemosensitivity through inhibition of the VLA-4/IL-10/PD-L1 pathway. Additionally, AS101 or SAS treatment of B16/F10 melanoma-bearing mice decreased tumor cell PD-L1 expression, leading to increased CD8+ T-cell infiltration into the tumors and tumor shrinkage. Combination treatment with an αPD-1 antibody and either tellurium compound significantly increased the antitumor efficacy of immunotherapy. Overall, VLA-4 integrin signaling is critical for tumor immune evasion and is a potential target for cancer treatment. Finally, AS101 or SAS, biologically active tellurium compounds, can effectively enhance the therapeutic efficacy of αPD-1-based cancer immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Telurio / Integrina alfa4beta1 / Antígeno B7-H1 Límite: Animals / Humans Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Australia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Telurio / Integrina alfa4beta1 / Antígeno B7-H1 Límite: Animals / Humans Idioma: En Revista: Int J Biol Sci Asunto de la revista: BIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Australia