Lung metastases share common immune features regardless of primary tumor origin
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.Met...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000491.full |
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| author | Victor Moreno Julián Pardo Ramon Salazar Sandra García-Mulero M Henar Alonso Cristina Santos Xavier Sanjuan Josep María Piulats Rebeca Sanz-Pamplona |
| author_facet | Victor Moreno Julián Pardo Ramon Salazar Sandra García-Mulero M Henar Alonso Cristina Santos Xavier Sanjuan Josep María Piulats Rebeca Sanz-Pamplona |
| author_sort | Victor Moreno |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0e80596774ee4294b6d2a2f79385cea5 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-0e80596774ee4294b6d2a2f79385cea52024-11-09T11:30:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000491Lung metastases share common immune features regardless of primary tumor originVictor Moreno0Julián Pardo1Ramon Salazar2Sandra García-Mulero3M Henar Alonso4Cristina Santos5Xavier Sanjuan6Josep María Piulats7Rebeca Sanz-Pamplona819 Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), L`Hospitalet del Llobregat, Barcelona, SpainCIBERES, CIBERINFEC, Instituto de Salud Carlos III, Madrid, Spain4 Department of Medical Oncology, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL)-CIBERONC, L`Hospitalet de Llobregat, Barcelona, Spain1 Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L`Hospitalet de Llobregat, Barcelona, Spain26 Cancer Prevention and Control Program, Catalan Institute of Oncology - IDIBELL, L`Hospitalet de Llobregat, Barcelona, Spain4 Department of Medical Oncology, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL)-CIBERONC, L`Hospitalet de Llobregat, Barcelona, Spain5 Department of Pathology, University Hospital Bellvitge (HUB-IDIBELL), L`Hospitalet de Llobregat, Barcelona, Spain4 Department of Medical Oncology, Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL)-CIBERONC, L`Hospitalet de Llobregat, Barcelona, Spain1 Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program (ODAP), Catalan Institute of Oncology (ICO), Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L`Hospitalet de Llobregat, Barcelona, SpainBackground 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.https://jitc.bmj.com/content/8/1/e000491.full |
| spellingShingle | Victor Moreno Julián Pardo Ramon Salazar Sandra García-Mulero M Henar Alonso Cristina Santos Xavier Sanjuan Josep María Piulats Rebeca Sanz-Pamplona Lung metastases share common immune features regardless of primary tumor origin Journal for ImmunoTherapy of Cancer |
| title | Lung metastases share common immune features regardless of primary tumor origin |
| title_full | Lung metastases share common immune features regardless of primary tumor origin |
| title_fullStr | Lung metastases share common immune features regardless of primary tumor origin |
| title_full_unstemmed | Lung metastases share common immune features regardless of primary tumor origin |
| title_short | Lung metastases share common immune features regardless of primary tumor origin |
| title_sort | lung metastases share common immune features regardless of primary tumor origin |
| url | https://jitc.bmj.com/content/8/1/e000491.full |
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