Open AccessBlood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial
Author(s) -
LazaBriviesca Raquel,
CruzBermúdez Alberto,
Nadal Ernest,
Insa Amelia,
GarcíaCampelo María del Rosario,
Huidobro Gerardo,
Dómine Manuel,
Majem Margarita,
RodríguezAbreu Delvys,
MartínezMartí 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,
SierraRodero Belén,
Tarín Carlos,
GarcíaGrande Aránzazu,
Haymaker Cara,
Wistuba Ignacio I.,
Romero Atocha,
Franco Fernando,
Provencio Mariano
Publication year - 2021
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.491
Subject(s) - medicine , chemoimmunotherapy , immune system , peripheral blood mononuclear cell , oncology , cd14 , nkg2d , il 2 receptor , immunotherapy , immunology , t cell , gastroenterology , cytotoxic t cell , biochemistry , chemistry , in vitro
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.