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Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients

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....

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Autores principales: Zhang, Tian, Pabla, Sarabjot, Lenzo, Felicia L., Conroy, Jeffrey M., Nesline, Mary K., Glenn, Sean T., Papanicolau-Sengos, Antonios, Burgher, Blake, Giamo, Vincent, Andreas, Jonathan, Wang, Yirong, Bshara, Wiam, Madden, Katherine G., Shirai, Keisuke, Dragnev, Konstantin, Tafe, Laura J., Gupta, Rajan, Zhu, Jason, Labriola, Matthew, McCall, Shannon, George, Daniel J., Ghatalia, Pooja, Dayyani, Farshid, Edwards, Robert, Park, Michelle S, Singh, Rajbir, Jacob, Robin, George, Saby, Xu, Bo, Zibelman, Matthew, Kurzrock, Razelle, Morrison, Carl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458647/
https://www.ncbi.nlm.nih.gov/pubmed/32923131
http://dx.doi.org/10.1080/2162402X.2020.1773200
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author Zhang, Tian
Pabla, Sarabjot
Lenzo, Felicia L.
Conroy, Jeffrey M.
Nesline, Mary K.
Glenn, Sean T.
Papanicolau-Sengos, Antonios
Burgher, Blake
Giamo, Vincent
Andreas, Jonathan
Wang, Yirong
Bshara, Wiam
Madden, Katherine G.
Shirai, Keisuke
Dragnev, Konstantin
Tafe, Laura J.
Gupta, Rajan
Zhu, Jason
Labriola, Matthew
McCall, Shannon
George, Daniel J.
Ghatalia, Pooja
Dayyani, Farshid
Edwards, Robert
Park, Michelle S
Singh, Rajbir
Jacob, Robin
George, Saby
Xu, Bo
Zibelman, Matthew
Kurzrock, Razelle
Morrison, Carl
author_facet Zhang, Tian
Pabla, Sarabjot
Lenzo, Felicia L.
Conroy, Jeffrey M.
Nesline, Mary K.
Glenn, Sean T.
Papanicolau-Sengos, Antonios
Burgher, Blake
Giamo, Vincent
Andreas, Jonathan
Wang, Yirong
Bshara, Wiam
Madden, Katherine G.
Shirai, Keisuke
Dragnev, Konstantin
Tafe, Laura J.
Gupta, Rajan
Zhu, Jason
Labriola, Matthew
McCall, Shannon
George, Daniel J.
Ghatalia, Pooja
Dayyani, Farshid
Edwards, Robert
Park, Michelle S
Singh, Rajbir
Jacob, Robin
George, Saby
Xu, Bo
Zibelman, Matthew
Kurzrock, Razelle
Morrison, Carl
author_sort Zhang, Tian
collection PubMed
description 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.
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spelling pubmed-74586472020-09-11 Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients Zhang, Tian Pabla, Sarabjot Lenzo, Felicia L. Conroy, Jeffrey M. Nesline, Mary K. Glenn, Sean T. Papanicolau-Sengos, Antonios Burgher, Blake Giamo, Vincent Andreas, Jonathan Wang, Yirong Bshara, Wiam Madden, Katherine G. Shirai, Keisuke Dragnev, Konstantin Tafe, Laura J. Gupta, Rajan Zhu, Jason Labriola, Matthew McCall, Shannon George, Daniel J. Ghatalia, Pooja Dayyani, Farshid Edwards, Robert Park, Michelle S Singh, Rajbir Jacob, Robin George, Saby Xu, Bo Zibelman, Matthew Kurzrock, Razelle Morrison, Carl Oncoimmunology Original Research 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. Taylor & Francis 2020-06-10 /pmc/articles/PMC7458647/ /pubmed/32923131 http://dx.doi.org/10.1080/2162402X.2020.1773200 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Zhang, Tian
Pabla, Sarabjot
Lenzo, Felicia L.
Conroy, Jeffrey M.
Nesline, Mary K.
Glenn, Sean T.
Papanicolau-Sengos, Antonios
Burgher, Blake
Giamo, Vincent
Andreas, Jonathan
Wang, Yirong
Bshara, Wiam
Madden, Katherine G.
Shirai, Keisuke
Dragnev, Konstantin
Tafe, Laura J.
Gupta, Rajan
Zhu, Jason
Labriola, Matthew
McCall, Shannon
George, Daniel J.
Ghatalia, Pooja
Dayyani, Farshid
Edwards, Robert
Park, Michelle S
Singh, Rajbir
Jacob, Robin
George, Saby
Xu, Bo
Zibelman, Matthew
Kurzrock, Razelle
Morrison, Carl
Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
title Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
title_full Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
title_fullStr Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
title_full_unstemmed Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
title_short Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
title_sort proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458647/
https://www.ncbi.nlm.nih.gov/pubmed/32923131
http://dx.doi.org/10.1080/2162402X.2020.1773200
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