Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splicing of FKBP51 immunophilin in melanoma patients
| العنوان: | Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splicing of FKBP51 immunophilin in melanoma patients |
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| المؤلفون: | Fortunato Ciardiello, Paolo D’ Arrigo, Emilio Francesco Giunta, Giuseppe Argenziano, Vincenza Vigorito, Martina Tufano, Teresa Troiani, Simona Romano, Maria Romano |
| المساهمون: | Troiani, Teresa, Giunta, Emilio Francesco, Tufano, Martina, Vigorito, Vincenza, D'Arrigo, Paolo, Argenziano, Giuseppe, Ciardiello, Fortunato, Romano, MARIA FIAMMETTA, Romano, Simona, Troiani, T., Giunta, E. F., Tufano, M., Vigorito, V., Arrigo, P. D., Argenziano, G., Ciardiello, F., Romano, M. F., Romano, S. |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Cancer Research, Immune receptor, Antibodies, Monoclonal, Humanized, Peripheral blood mononuclear cell, T-Lymphocytes, Regulatory, Article, B7-H1 Antigen, Flow cytometry, Tacrolimus Binding Proteins, 03 medical and health sciences, Prognostic markers, 0302 clinical medicine, Immunophenotyping, Immune system, medicine, Gene silencing, Humans, Protein Isoforms, Melanoma, Immune Checkpoint Inhibitors, 030304 developmental biology, Aged, 0303 health sciences, medicine.diagnostic_test, business.industry, Monocyte, Macrophages, Macrophage Activation, Middle Aged, medicine.disease, medicine.anatomical_structure, Nivolumab, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, Female, Immunotherapy, business |
| الوصف: | Background FKBP51 immunophilin is abundantly expressed by immune cells. Co-inhibitory immune receptor signalling generates the splicing isoform FKBP51s. Tregs stained by FKBP51s are increased in melanoma patients and their counts are associated with anti-CTLA-4 response. An expansion of FKBP51s+PD-L1+ monocytes was measured in a group of non-responding patients to anti-CTLA-4. The aim of this work was to confirm the predictive value of response of FKBP51s+Tregs in a cohort of patients undergoing anti-PD1 treatment and shed light on a monocyte subset co-expressing PD-L1/FKBP51s. Methods Co-cultures of organoids and autologous lymphocytes were used to confirm that tumour T-cell interaction can induce FKBP51s. PBMC immunophenotype and flow cytometry served to assess and monitor FKBP51s+Treg and FKBP51s+PD-L1+ monocytes in 22 advanced melanoma patients treated with anti-PD1. Silencing and overexpression of FKBP51s in human macrophages served to address the protein role in the tolerant macrophages’ behaviour. Results FKBP51s+Tregs count was increased in responders and had a prognostic value. Non-responders showed an early increase in FKBP51s+ PD-L1+ monocytes during anti-PD1 treatment. Manipulation of FKBP51s modulated the macrophage–phenotype, with forced protein expression promoting aspects associated with tolerance. Conclusions FKBP51s may guide in the selection and monitoring of melanoma patient candidates to immune-checkpoint-targeted therapy. Manipulation of FKBP51s may overcome resistance. |
| اللغة: | English |
| تدمد: | 1532-1827 0007-0920 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::08ae742bb21cf58f5c7b1918c9a43b2bTest http://europepmc.org/articles/PMC7283486Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....08ae742bb21cf58f5c7b1918c9a43b2b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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