Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
| Autor: | Sean T. Glenn, Antonios Papanicolau-Sengos, Jeffrey M. Conroy, Blake Burgher, Keisuke Shirai, Carl Morrison, Rajan T. Gupta, Jason Zhu, Konstantin H. Dragnev, Pooja Ghatalia, Razelle Kurzrock, Mary Nesline, Saby George, Vincent Giamo, Wiam Bshara, Tian Zhang, Felicia L. Lenzo, Katherine G. Madden, Matthew Labriola, Bo Xu, Michelle S Park, Matthew Zibelman, Jonathan Andreas, Rajbir Singh, Robert Edwards, Daniel J. George, Shannon J. McCall, Robin Jacob, Yirong Wang, Laura J. Tafe, Farshid Dayyani, Sarabjot Pabla |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Kidney Disease Immune checkpoint inhibitors medicine.medical_treatment urologic and male genital diseases 0302 clinical medicine Antineoplastic Agents Immunological Renal cell carcinoma PD-1 Immunology and Allergy Medicine RC254-282 Original Research Cancer biology ki-67 pd-1 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Middle Aged Progression-Free Survival Immunological Nivolumab Oncology 030220 oncology & carcinogenesis Ki-67 Immunohistochemistry Female Immunotherapy Research Article Adult PD-L1 renal cell carcinoma proliferation Immunology Oncology and Carcinogenesis Antineoplastic Agents 03 medical and health sciences pd-l1 Genetics Humans Carcinoma Renal Cell Aged nivolumab business.industry Carcinoma Renal Cell RC581-607 medicine.disease Clear cell renal cell carcinoma 030104 developmental biology Good Health and Well Being Cancer research biology.protein Immunologic diseases. Allergy business |
| Zdroj: | Oncoimmunology, vol 9, iss 1 OncoImmunology, Vol 9, Iss 1 (2020) Oncoimmunology article-version (VoR) Version of Record |
| Popis: | Background Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings. |
| Databáze: | OpenAIRE |
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