Lung metastases share common immune features regardless of primary tumor origin.
J Immunother Cancer
; 8(1)2020 06.
Article
en En
| MEDLINE
| ID: mdl-32591432
ABSTRACT
BACKGROUND:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Microambiente Tumoral
/
Inmunoterapia
/
Pulmón
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Año:
2020
Tipo del documento:
Article
País de afiliación:
España