Impacts of pembrolizumab therapy on immune phenotype in patients with high-grade neuroendocrine neoplasms
| العنوان: | Impacts of pembrolizumab therapy on immune phenotype in patients with high-grade neuroendocrine neoplasms |
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| المؤلفون: | Kerry S. Campbell, R. Katherine Alpaugh, Alexander W. MacFarlane, Ho Man Yeung, Paul F. Engstrom, Essel Dulaimi, Arvind Dasari, Namrata Vijayvergia |
| المصدر: | Cancer Immunol Immunother |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Programmed Cell Death 1 Receptor, Immunology, Pembrolizumab, Antibodies, Monoclonal, Humanized, Article, Flow cytometry, Antineoplastic Agents, Immunological, Lymphocytes, Tumor-Infiltrating, TIGIT, Internal medicine, Biomarkers, Tumor, medicine, Humans, Immunology and Allergy, Prospective Studies, Receptors, Immunologic, Aged, biology, medicine.diagnostic_test, Tumor-infiltrating lymphocytes, business.industry, CD69, Middle Aged, Prognosis, medicine.disease, Peripheral, Gene Expression Regulation, Neoplastic, Survival Rate, Neuroendocrine Tumors, biology.protein, Female, Antibody, business, Progressive disease, Follow-Up Studies |
| الوصف: | High grade neuroendocrine neoplasms (G3 NENs) are rare aggressive tumors with limited treatment options. Twenty-one previously treated patients with metastatic extra-pulmonary G3 NENs were treated with pembrolizumab. Baseline tumor samples were assessed for PD-L1 and tumor infiltrating lymphocytes (TIL). Peripheral blood samples drawn pre-treatment, prior to cycle three, and at disease progression were analyzed by flow cytometry. One patient achieved partial response, two had stable disease, and 18 exhibited progressive disease. The partially responding patient did not progress after 392 days, and the median progression-free survival (PFS) was 59 days. Longer PFS correlated independently with higher pre-treatment peripheral blood T-cell counts and lower pre-treatment activation state (CD69 expression) of naive T cells and NK cells. Peripheral T-cell viability was reduced in patients with greater TILs. Post-treatment, T cells had reduced numbers of CD4+ cells, reduced PD-1 expression, increased activation of effector (CD62L−) cells, and increased expression of TIGIT. Baseline TIGIT expression on peripheral T cells also correlated positively with Ki67 in tumor. Patients with higher baseline T-cell expression of TIM-3 had shorter PFS. Despite limited activity of pembrolizumab, this study highlights the immune phenotype in this rare tumor type before and after treatment. High baseline peripheral T-cell count and reduced activation of T and NK cell subsets were associated with improved outcomes. Furthermore, increased post-treatment TIGIT and elevated baseline TIM-3 expression suggest that these may limit the efficacy of pembrolizumab, providing a rationale for combination immunotherapy (PD-1 with TIGIT and/or TIM-3 antibodies) to treat extra-pulmonary G3 NENs. |
| تدمد: | 1432-0851 0340-7004 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::427872e9fa04075bcec253b57f12b396Test https://doi.org/10.1007/s00262-020-02811-5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....427872e9fa04075bcec253b57f12b396 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320851 03407004 |
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