000095551 001__ 95551
000095551 005__ 20210902121737.0
000095551 0247_ $$2doi$$a10.1136/jitc-2019-000491
000095551 0248_ $$2sideral$$a119607
000095551 037__ $$aART-2020-119607
000095551 041__ $$aeng
000095551 100__ $$aGarcía-Mulero, S.
000095551 245__ $$aLung metastases share common immune features regardless of primary tumor origin
000095551 260__ $$c2020
000095551 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095551 5203_ $$aBACKGROUND: Only certain disseminated cells are able to grow in secondary organs to create a metastatic tumor. Under the hypothesis that the immune microenvironment of the host tissue may play an important role in this process, we have categorized metastatic samples based on their immune features. METHODS: Gene expression data of metastatic samples (n=374) from four secondary sites (brain, bone, liver and lung) were used to characterize samples based on their immune and stromal infiltration using gene signatures and cell quantification tools. A clustering analysis was done that separated metastatic samples into three different immune categories: high, medium and low. RESULTS: Significant differences were found between the immune profiles of samples metastasizing in distinct organs. Metastases in lung showed a higher immunogenic score than metastases in brain, liver or bone, regardless of their primary site of origin. Also, they preferentially clustered in the high immune group. Samples in this cluster exhibited a clear inflammatory phenotype, higher levels of immune infiltrate, overexpression of programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathways and upregulation of genes predicting clinical response to programmed cell death protein 1 (PD-1) blockade (T-cell inflammatory signature). A decision tree algorithm was used to select CD74 as a biomarker that identify samples belonging to this high-immune subtype of metastases, having specificity of 0.96 and sensitivity of 1. CONCLUSIONS: We have found a group of lung-enriched metastases showing an inflammatory phenotype susceptible to be treated with immunotherapy.
000095551 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000095551 590__ $$a13.751$$b2020
000095551 591__ $$aONCOLOGY$$b15 / 242 = 0.062$$c2020$$dQ1$$eT1
000095551 591__ $$aIMMUNOLOGY$$b8 / 162 = 0.049$$c2020$$dQ1$$eT1
000095551 592__ $$a5.059$$b2020
000095551 593__ $$aCancer Research$$c2020$$dQ1
000095551 593__ $$aImmunology$$c2020$$dQ1
000095551 593__ $$aPharmacology$$c2020$$dQ1
000095551 593__ $$aMolecular Medicine$$c2020$$dQ1
000095551 593__ $$aOncology$$c2020$$dQ1
000095551 593__ $$aImmunology and Allergy$$c2020$$dQ1
000095551 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095551 700__ $$aAlonso, M.H.
000095551 700__ $$0(orcid)0000-0003-0154-0730$$aPardo, J.$$uUniversidad de Zaragoza
000095551 700__ $$aSantos, C.
000095551 700__ $$aSanjuan, X.
000095551 700__ $$aSalazar, R.
000095551 700__ $$aMoreno, V.
000095551 700__ $$aPiulats, J.M.
000095551 700__ $$aSanz-Pamplona, R.
000095551 7102_ $$11011$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Inmunología
000095551 773__ $$g8, 1 (2020), e000491 1-12$$pJ. immunotherap. cancer$$tJournal for ImmunoTherapy of Cancer$$x2051-1426
000095551 8564_ $$s5985575$$uhttps://zaguan.unizar.es/record/95551/files/texto_completo.pdf$$yVersión publicada
000095551 8564_ $$s94807$$uhttps://zaguan.unizar.es/record/95551/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095551 909CO $$ooai:zaguan.unizar.es:95551$$particulos$$pdriver
000095551 951__ $$a2021-09-02-09:40:23
000095551 980__ $$aARTICLE