학술논문
The soluble form of CD160 acts as a tumor mediator of immune escape in melanoma.
Document Type
Academic Journal
Author
Gauci ML; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Giustiniani J; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Lepelletier C; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Garbar C; Institute Godinot, Reims, France.; Thonnart N; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Dumaz N; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Foussat A; Alderaan Biotechnology, Paris, France.; Lebbé C; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Department of Dermatology, AP-HP, Saint-Louis Hospital, Paris, France.; Bensussan A; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France.; Université Paris Cité, IRSL, Paris, France.; Institute Godinot, Reims, France.; Marie-Cardine A; INSERM U976, HIPI, Team 1 'Onco-Dermatology and Therapies', Saint Louis Hospital, 1 avenue Claude Vellefaux, 75010, Paris, France. anne.marie-cardine@inserm.fr.
Source
Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8605732 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0851 (Electronic) Linking ISSN: 03407004 NLM ISO Abbreviation: Cancer Immunol Immunother Subsets: MEDLINE
Subject
Language
English
Abstract
Melanoma is responsible for 90% of skin cancer-related deaths. Major therapeutic advances have led to a considerable improvement in the prognosis of patients, with the development of targeted therapies (BRAF or MEK inhibitors) and immunotherapy (anti-CTLA-4 or -PD-1 antibodies). However, the tumor constitutes an immunosuppressive microenvironment that prevents the therapeutic efficacy and/or promotes the development of secondary resistances. CD160 is an activating NK-cell receptor initially described as delineating the NK and CD8 + T-cell cytotoxic populations. Three forms of CD160 have been described: (1) the GPI isoform, constitutively expressed and involved in the initiation of NK-cells' cytotoxic activity, (2) the transmembrane isoform, neo-synthesized upon cell activation, allowing the amplification of NK cells' cytotoxic functions and (3) the soluble form, generated after cleavage of the GPI isoform, which presents an immuno-suppressive activity. By performing immunohistochemistry analyses, we observed a strong expression of CD160 at the primary cutaneous tumor site of melanoma patients. We further demonstrated that melanoma cells express CD160-GPI isoform and constitutively release the soluble form (sCD160) into the tumor environment. sCD160 was shown to inhibit the cytotoxic activity of NK-cells towards their target cells. In addition, it was found in the serum of melanoma patients and associated with increased tumor dissemination. Altogether these results support a role for sCD160 in the mechanisms leading to the inhibition of anti-tumor response and immune surveillance in melanoma.
(© 2022. The Author(s).)
(© 2022. The Author(s).)