dc.creator | Sierra Rodero, Belén | es |
dc.creator | Cruz Bermúdez, Alberto | es |
dc.creator | Nadal, Ernest | es |
dc.creator | Bernabé-Caro, Reyes | es |
dc.creator | Provencio, Mariano | es |
dc.date.accessioned | 2022-09-06T17:22:00Z | |
dc.date.available | 2022-09-06T17:22:00Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | Sierra Rodero, B., Cruz Bermúdez, A., Nadal, E., Bernabé-Caro, R. y Provencio, M. (2021). Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial. Journal for immunotherapy of cancer, 9 (8), 1-13. | |
dc.identifier.issn | 2051-1426 | es |
dc.identifier.uri | https://hdl.handle.net/11441/136804 | |
dc.description.abstract | Background Pneumonitis (Pn) is one of the main immune-related adverse effects, having a special
importance in lung cancer, since they share affected tissue. Despite its clinical relevance, Pn development
remains an unpredictable treatment adverse effect, whose mechanisms are mainly unknown, being even more
obscure when it is associated to chemoimmunotherapy.Methods In order to identify parameters associated to
treatment related Pn, we analyzed clinical variables and molecular parameters from 46 patients with potentially resectable stage IIIA non-small-cell lung cancer treated with neoadjuvant chemoimmunotherapy included in the NADIM clinical trial (NCT03081689). Pn was defined as clinical or radiographic evidence of lung inflammation without alternative diagnoses, from treatment initiation to 180 days.
Results Among 46 patients, 12 developed Pn (26.1%). Sex, age, smoking status, packs-year, histological
subtype, clinical or pathological response, progression free survival, overall survival and number of nivolumab
cycles, were not associated to Pn development. Regarding molecular parameters at diagnosis, Pn evelopment
was not associated to programmed death ligand 1, TPS, T cell receptor repertoire parameters, or tumor
mutational burden. However, patients who developed Pn had statistically significant lower blood median levels of platelet to monocyte ratio (p=0.012) and teratocarcinoma derived growth factor 1 (p=0.013; area under the curve (AUC) 0.801), but higher median percentages of natural killers (NKs) (p=0.019; AUC 0.786), monocytes (p=0.017; AUC 0.791), MSP (p=0.006; AUC 0.838), PARN (p=0.017; AUC 0.790), and E-Cadherin (p=0.022; AUC 0.788). In addition, the immune scenario of Pn after neoadjuvant treatment involves: high levels of neutrophils and NK cells, but low levels of B and T cells in peripheral blood; increased clonality of intratumoral T cells; and elevated plasma levels of several growth factors (EGF, HGF, VEGF, ANG-1, PDGF, NGF, and NT4) and inflammatory cytokines (MIF, CCL16, neutrophil gelatinase-associated lipocalin, BMP-4, and u-PAR).
Conclusions Although statistically underpowered, our results shed light on the possible mechanisms behind Pn development, involving innate and adaptative immunity, and open the possibility to predict patients at high risk. If confirmed, this may allow the personalization of both, the surveillance strategy and the therapeutic approaches to manage Pn in patients receiving chemoimmunotherapy . | es |
dc.format | application/pdf | es |
dc.format.extent | 13 | es |
dc.language.iso | eng | es |
dc.publisher | BMC | es |
dc.relation.ispartof | Journal for immunotherapy of cancer, 9 (8), 1-13. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Molecular parameters | es |
dc.subject | Clinical parameters | es |
dc.subject | Pneumonitis | es |
dc.subject | Cancer | es |
dc.subject | Chemoimmunotherapy | es |
dc.title | Clinical and molecular parameters associated to pneumonitis development in non-small-cell lung cancer patients receiving chemoimmunotherapy from NADIM trial | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | https://jitc.bmj.com/content/9/8/e002804 | es |
dc.identifier.doi | 10.1136/jitc-2021-002804 | es |
dc.journaltitle | Journal for immunotherapy of cancer | es |
dc.publication.volumen | 9 | es |
dc.publication.issue | 8 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 13 | es |