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Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial

BACKGROUND: Immunotherapy is being tested in early‐stage non‐small cell lung cancer (NSCLC), and achieving higher rates of complete pathological responses (CPR) as compared to standard of care. Early identification of CPR patients has vital clinical implications. In this study, we focused on basal p...

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Autores principales: Laza‐Briviesca, Raquel, Cruz‐Bermúdez, Alberto, Nadal, Ernest, Insa, Amelia, García‐Campelo, María del Rosario, Huidobro, Gerardo, Dómine, Manuel, Majem, Margarita, Rodríguez‐Abreu, Delvys, Martínez‐Martí, Alex, De Castro Carpeño, Javier, Cobo, Manuel, López Vivanco, Guillermo, Del Barco, Edel, Bernabé Caro, Reyes, Viñolas, Nuria, Barneto Aranda, Isidoro, Viteri, Santiago, Massuti, Bartomeu, Casarrubios, Marta, Sierra‐Rodero, Belén, Tarín, Carlos, García‐Grande, Aránzazu, Haymaker, Cara, Wistuba, Ignacio I., Romero, Atocha, Franco, Fernando, Provencio, Mariano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288017/
https://www.ncbi.nlm.nih.gov/pubmed/34323406
http://dx.doi.org/10.1002/ctm2.491
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author Laza‐Briviesca, Raquel
Cruz‐Bermúdez, Alberto
Nadal, Ernest
Insa, Amelia
García‐Campelo, María del Rosario
Huidobro, Gerardo
Dómine, Manuel
Majem, Margarita
Rodríguez‐Abreu, Delvys
Martínez‐Martí, Alex
De Castro Carpeño, Javier
Cobo, Manuel
López Vivanco, Guillermo
Del Barco, Edel
Bernabé Caro, Reyes
Viñolas, Nuria
Barneto Aranda, Isidoro
Viteri, Santiago
Massuti, Bartomeu
Casarrubios, Marta
Sierra‐Rodero, Belén
Tarín, Carlos
García‐Grande, Aránzazu
Haymaker, Cara
Wistuba, Ignacio I.
Romero, Atocha
Franco, Fernando
Provencio, Mariano
author_facet Laza‐Briviesca, Raquel
Cruz‐Bermúdez, Alberto
Nadal, Ernest
Insa, Amelia
García‐Campelo, María del Rosario
Huidobro, Gerardo
Dómine, Manuel
Majem, Margarita
Rodríguez‐Abreu, Delvys
Martínez‐Martí, Alex
De Castro Carpeño, Javier
Cobo, Manuel
López Vivanco, Guillermo
Del Barco, Edel
Bernabé Caro, Reyes
Viñolas, Nuria
Barneto Aranda, Isidoro
Viteri, Santiago
Massuti, Bartomeu
Casarrubios, Marta
Sierra‐Rodero, Belén
Tarín, Carlos
García‐Grande, Aránzazu
Haymaker, Cara
Wistuba, Ignacio I.
Romero, Atocha
Franco, Fernando
Provencio, Mariano
author_sort Laza‐Briviesca, Raquel
collection PubMed
description BACKGROUND: Immunotherapy is being tested in early‐stage non‐small cell lung cancer (NSCLC), and achieving higher rates of complete pathological responses (CPR) as compared to standard of care. Early identification of CPR patients has vital clinical implications. In this study, we focused on basal peripheral immune cells and their treatment‐related changes to find biomarkers associated to CPR. METHODS: Blood from 29 stage IIIA NSCLC patients participating in the NADIM trial (NCT03081689) was collected at diagnosis and post neoadjuvant treatment. More than 400 parameters of peripheral blood mononuclear cells (PBMCs) phenotype and plasma soluble factors were analyzed. RESULTS: Neoadjuvant chemoimmunotherapy altered more than 150 immune parameters. At diagnosis, 11 biomarkers associated to CPR were described, with an area under the ROC curve >0.70 and p‐value <.05. CPR patients had significantly higher levels of CD4(+)PD‐1(+) cells, NKG2D, and CD56 expression on T CD56 cells, intensity of CD25 expression on CD4(+)CD25hi(+) cells and CD69 expression on intermediate monocytes; but lower levels of CD3(+)CD56(–)CTLA‐4(+) cells, CD14(++)CD16(+)CTLA‐4(+) cells, CTLA‐4 expression on T CD56 cells and lower levels of b‐NGF, NT‐3, and VEGF‐D in plasma compared to non‐CPR. Post treatment, CPR patients had significantly higher levels of CD19 expression on B cells, BCMA, 4‐1BB, MCSF, and PARC and lower levels of MPIF‐1 and Flt‐3L in plasma compared to non‐CPR. CONCLUSIONS: Patients achieving CPR seem to have a distinctive peripheral blood immune status at diagnosis, even showing different immune response to treatment. These results reinforce the different biology behind CPR and non‐CPR responses.
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spelling pubmed-82880172021-07-21 Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial Laza‐Briviesca, Raquel Cruz‐Bermúdez, Alberto Nadal, Ernest Insa, Amelia García‐Campelo, María del Rosario Huidobro, Gerardo Dómine, Manuel Majem, Margarita Rodríguez‐Abreu, Delvys Martínez‐Martí, Alex De Castro Carpeño, Javier Cobo, Manuel López Vivanco, Guillermo Del Barco, Edel Bernabé Caro, Reyes Viñolas, Nuria Barneto Aranda, Isidoro Viteri, Santiago Massuti, Bartomeu Casarrubios, Marta Sierra‐Rodero, Belén Tarín, Carlos García‐Grande, Aránzazu Haymaker, Cara Wistuba, Ignacio I. Romero, Atocha Franco, Fernando Provencio, Mariano Clin Transl Med Research Articles BACKGROUND: Immunotherapy is being tested in early‐stage non‐small cell lung cancer (NSCLC), and achieving higher rates of complete pathological responses (CPR) as compared to standard of care. Early identification of CPR patients has vital clinical implications. In this study, we focused on basal peripheral immune cells and their treatment‐related changes to find biomarkers associated to CPR. METHODS: Blood from 29 stage IIIA NSCLC patients participating in the NADIM trial (NCT03081689) was collected at diagnosis and post neoadjuvant treatment. More than 400 parameters of peripheral blood mononuclear cells (PBMCs) phenotype and plasma soluble factors were analyzed. RESULTS: Neoadjuvant chemoimmunotherapy altered more than 150 immune parameters. At diagnosis, 11 biomarkers associated to CPR were described, with an area under the ROC curve >0.70 and p‐value <.05. CPR patients had significantly higher levels of CD4(+)PD‐1(+) cells, NKG2D, and CD56 expression on T CD56 cells, intensity of CD25 expression on CD4(+)CD25hi(+) cells and CD69 expression on intermediate monocytes; but lower levels of CD3(+)CD56(–)CTLA‐4(+) cells, CD14(++)CD16(+)CTLA‐4(+) cells, CTLA‐4 expression on T CD56 cells and lower levels of b‐NGF, NT‐3, and VEGF‐D in plasma compared to non‐CPR. Post treatment, CPR patients had significantly higher levels of CD19 expression on B cells, BCMA, 4‐1BB, MCSF, and PARC and lower levels of MPIF‐1 and Flt‐3L in plasma compared to non‐CPR. CONCLUSIONS: Patients achieving CPR seem to have a distinctive peripheral blood immune status at diagnosis, even showing different immune response to treatment. These results reinforce the different biology behind CPR and non‐CPR responses. John Wiley and Sons Inc. 2021-07-19 /pmc/articles/PMC8288017/ /pubmed/34323406 http://dx.doi.org/10.1002/ctm2.491 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Laza‐Briviesca, Raquel
Cruz‐Bermúdez, Alberto
Nadal, Ernest
Insa, Amelia
García‐Campelo, María del Rosario
Huidobro, Gerardo
Dómine, Manuel
Majem, Margarita
Rodríguez‐Abreu, Delvys
Martínez‐Martí, Alex
De Castro Carpeño, Javier
Cobo, Manuel
López Vivanco, Guillermo
Del Barco, Edel
Bernabé Caro, Reyes
Viñolas, Nuria
Barneto Aranda, Isidoro
Viteri, Santiago
Massuti, Bartomeu
Casarrubios, Marta
Sierra‐Rodero, Belén
Tarín, Carlos
García‐Grande, Aránzazu
Haymaker, Cara
Wistuba, Ignacio I.
Romero, Atocha
Franco, Fernando
Provencio, Mariano
Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
title Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
title_full Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
title_fullStr Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
title_full_unstemmed Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
title_short Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
title_sort blood biomarkers associated to complete pathological response on nsclc patients treated with neoadjuvant chemoimmunotherapy included in nadim clinical trial
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288017/
https://www.ncbi.nlm.nih.gov/pubmed/34323406
http://dx.doi.org/10.1002/ctm2.491
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