Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC)
| العنوان: | Genetic Variants and Tumor Immune Microenvironment: Clues for Targeted Therapies in Inflammatory Breast Cancer (IBC) |
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| المؤلفون: | Rajeswari Nagarathinam, Michael Slifker, Katherine Alpaugh, Jianming Pei, Kathy Q. Cai, Yulan Gong, Massimo Cristofanilli, Elias Obeid, Zachary Hasse, Christopher Sebastiano, Jennifer S. Winn, Sandra V. Fernandez, Eric A. Ross, Lorenzo Gerratana, Julio E. Noriega, Maria F. Arisi |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 8924, p 8924 (2021) Volume 22 Issue 16 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | programmed cell death-ligand 1 (PD-L1), tumor infiltrating lymphocytes (TILs), Receptor, ErbB-2, medicine.medical_treatment, B7-H1 Antigen, Tumor Microenvironment, poly (ADP-ribose) polymerase, Molecular Targeted Therapy, Biology (General), skin and connective tissue diseases, immune checkpoint inhibitors (ICIs), Spectroscopy, CD20, biology, FOXP3, High-Throughput Nucleotide Sequencing, General Medicine, Middle Aged, Prognosis, Computer Science Applications, Gene Expression Regulation, Neoplastic, Survival Rate, Chemistry, Receptors, Estrogen, PARP inhibitor, Immunohistochemistry, RAD51C, Female, Inflammatory Breast Neoplasms, Receptors, Progesterone, Cell-Free Nucleic Acids, Adult, QH301-705.5, PALB2, Inflammatory breast cancer, Catalysis, Article, Inorganic Chemistry, Lymphocytes, Tumor-Infiltrating, medicine, Biomarkers, Tumor, cell-free DNA (cfDNA), Humans, Physical and Theoretical Chemistry, Molecular Biology, QD1-999, Aged, Retrospective Studies, business.industry, Organic Chemistry, Immunotherapy, medicine.disease, Mutation, biology.protein, Cancer research, business, Follow-Up Studies |
| الوصف: | To better understand the etiology of inflammatory breast cancer (IBC) and identify potential therapies, we studied genomic alterations in IBC patients. Targeted, next-generation sequencing (NGS) was performed on cell-free DNA (cfDNA) (n = 33) and paired DNA from tumor tissues (n = 29) from 32 IBC patients. We confirmed complementarity between cfDNA and tumor tissue genetic profiles. We found a high incidence of germline variants in IBC patients that could be associated with an increased risk of developing the disease. Furthermore, 31% of IBC patients showed deficiencies in the homologous recombination repair (HRR) pathway (BRCA1, BRCA2, PALB2, RAD51C, ATM, BARD1) making them sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. We also characterized the tumor-infiltrating lymphocytes (TILs) in tumor tissue biopsies by studying several markers (CD4, CD8, FoxP3, CD20, PD-1, and PD-L1) through immunohistochemistry (IHC) staining. In 7 of 24 (29%) patients, tumor biopsies were positive for PD-L1 and PD-1 expression on TILs, making them sensitive to PD-1/PD-L1 blocking therapies. Our results provide a rationale for considering PARP inhibitors and PD-1/PDL1 blocking immunotherapy in qualifying IBC patients. |
| وصف الملف: | application/pdf |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b574cfb17b2590c27702c1cc7e4f4b8Test https://pubmed.ncbi.nlm.nih.gov/34445631Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4b574cfb17b2590c27702c1cc7e4f4b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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