Lung metastases share common immune features regardless of primary tumor origin

Abstract

BackgroundOnly 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.MethodsGene 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.ResultsSignificant 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.ConclusionsWe have found a group of lung-enriched metastases showing an inflammatory phenotype susceptible to be treated with immunotherapy.

Metastatic Colonization: Escaping Immune Surveillance

“…Thus, the immune populations recruited in response to DTCs may greatly differ across organs. Interestingly, recent work showed that lung metastases have a higher immunogenic signature compared to metastases in bone, liver and brain [48]. Although a wide heterogeneity in metastatic immune environment, lung metastatic samples exhibited increased lymphocyte and DC infiltration consistent with the active local immune system in lungs [48].…”

“…Interestingly, recent work showed that lung metastases have a higher immunogenic signature compared to metastases in bone, liver and brain [ 48 ]. Although a wide heterogeneity in metastatic immune environment, lung metastatic samples exhibited increased lymphocyte and DC infiltration consistent with the active local immune system in lungs [ 48 ]. In addition, immunogenic profiles in liver and brain metastases appeared to be independent of the primary tumor origin.…”

“…In addition, immunogenic profiles in liver and brain metastases appeared to be independent of the primary tumor origin. This study suggests that the host organ of metastases has a notable effect on the local immune infiltrates [ 48 ]. Thus, immunotherapy guidelines may be based on metastatic immune signature rather than on the tumor of origin.…”

Prognostic and predictive value of FCER1G in glioma outcomes and response to immunotherapy

“…Gene Set Enrichment Analysis (GSEA) was further used to investigate the functional enrichment with R package "Pi" (23). To explore the correlation between the expression levels of FCER1G and immune status, a total of 25 immunity-related gene sets covering both innate and adaptive responses were from a previous study (24)(Supplementary materials). Gene Set Variation Analysis from R package GSVA (20) was performed to obtain the immune pro le of the glioma samples.…”

“…To predict their putative response to anti-PDL1 drug, glioma samples were scored with the GSVA method using the T-cell in ammatory (TIS) signature. This signature was derived from a previous study (24) and listed in Supplementary Materials.…”