Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Background Despite the prominent role of innate immunity in the antitumor response, little is known about the myeloid composition of human non-small cell lung cancer (NSCLC) with respect to histology and molecular subtype. We used multiplexed quantitative immunofluorescence (QIF) to measure the dist...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2022-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/7/e005025.full |
| _version_ | 1811325734589825024 |
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| author | Roy S Herbst Lieping Chen David L Rimm Miguel F Sanmamed Kurt A Schalper Alice Li Konstantinos Syrigos Jovian Yu Adam Aguirre-Ducler Brian S Henick Franz Villarroel-Espindola Ila Datar Shruti Desai |
| author_facet | Roy S Herbst Lieping Chen David L Rimm Miguel F Sanmamed Kurt A Schalper Alice Li Konstantinos Syrigos Jovian Yu Adam Aguirre-Ducler Brian S Henick Franz Villarroel-Espindola Ila Datar Shruti Desai |
| author_sort | Roy S Herbst |
| collection | DOAJ |
| description | Background Despite the prominent role of innate immunity in the antitumor response, little is known about the myeloid composition of human non-small cell lung cancer (NSCLC) with respect to histology and molecular subtype. We used multiplexed quantitative immunofluorescence (QIF) to measure the distribution and clinical significance of major myeloid cell subsets in large retrospective NSCLC collections.Methods We established a QIF panel to map major myeloid cell subsets in fixed human NSCLC including 4’,6-Diamidino-2-Phenylindole for all cells, pancytokeratin for tumor-epithelial cells, CD68 for M1-like macrophages; and CD11b plus HLA-DR to interrogate mature and immature myeloid cell populations such as myeloid derived suppressor cells (MDSCs). We interrogated 793 NSCLCs represented in four tissue microarray-based cohorts: #1 (Yale, n=379) and #2 (Greece, n=230) with diverse NSCLC subtypes; #3 (Yale, n=138) with molecularly annotated lung adenocarcinomas (ADC); and #4 (Yale, n=46) with patient-matched NSCLC and morphologically-normal lung tissue. We examined associations between marker levels, myeloid cell profiles, clinicopathologic/molecular variables and survival.Results The levels of CD68+ M1 like macrophages were significantly lower and the fraction of CD11b+/HLA-DR− MDSC-like cells was prominently higher in tumor than in matched non-tumor lung tissues. HLA-DR was consistently higher in myeloid cells from tumors with elevated CD68 expression. Stromal CD11b was significantly higher in squamous cell carcinomas (SCC) than in ADC across the cohorts and EGFR-mutated lung ADCs displayed lower CD11b levels than KRAS-mutant tumors. Increased stromal CD68- and HLA-DR-expressing cells was associated with better survival in ADCs from two independent NSCLC cohorts. In SCC, increased stromal CD11b or HLA-DR expression was associated with a trend towards shorter 5-year survival.Conclusions NSCLCs display an unfavorable myeloid immune contexture relative to non-tumor lung and exhibit distinct myeloid-cell profiles across histologies and presence of major oncogenic driver-mutations. Elevated M1-like stromal proinflammatory myeloid cells are prognostic in lung ADC, but not in SCC. |
| first_indexed | 2024-04-13T14:37:54Z |
| format | Article |
| id | doaj.art-8666dac9e47e49ac8886f836aa022847 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-04-13T14:37:54Z |
| publishDate | 2022-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-8666dac9e47e49ac8886f836aa0228472022-12-22T02:42:59ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-07-0110710.1136/jitc-2022-005025Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancerRoy S Herbst0Lieping Chen1David L Rimm2Miguel F Sanmamed3Kurt A Schalper4Alice Li5Konstantinos Syrigos6Jovian Yu7Adam Aguirre-Ducler8Brian S Henick9Franz Villarroel-Espindola10Ila Datar11Shruti Desai12Medical Oncology, Yale Cancer Center | Yale School of Medicine | Smilow Cancer Hospital at Yale New Haven, New Haven, Connecticut, USAAff5 grid.47100.320000000419368710Yale University New Haven CT USADepartment of Pathology, Yale University School of Medicine, New Haven, Connecticut, USAImmunology and Immunotherapy, Center for Applied Medical Research (CIMA). University of Navarra, Pamplona, SpainPathology, Yale School of Medicine, New Haven, Connecticut, USA2University of Cambridge, School of Clinical Medicine, Cambridge, UK3rd Department of Medicine, National and Kapodistrian University of Athens, Athens, Attica, GreeceDepartment of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, Illinois, USAPathology, Yale School of Medicine, New Haven, Connecticut, USAMedicine, Columbia University Irving Medical Center, New York, New York, USADepartment of Pathology, Yale School of Medicine, New Haven, Connecticut, USADepartment of Pathology, Yale School of Medicine, New Haven, Connecticut, USAYale Cancer Center, New Haven, Connecticut, USABackground Despite the prominent role of innate immunity in the antitumor response, little is known about the myeloid composition of human non-small cell lung cancer (NSCLC) with respect to histology and molecular subtype. We used multiplexed quantitative immunofluorescence (QIF) to measure the distribution and clinical significance of major myeloid cell subsets in large retrospective NSCLC collections.Methods We established a QIF panel to map major myeloid cell subsets in fixed human NSCLC including 4’,6-Diamidino-2-Phenylindole for all cells, pancytokeratin for tumor-epithelial cells, CD68 for M1-like macrophages; and CD11b plus HLA-DR to interrogate mature and immature myeloid cell populations such as myeloid derived suppressor cells (MDSCs). We interrogated 793 NSCLCs represented in four tissue microarray-based cohorts: #1 (Yale, n=379) and #2 (Greece, n=230) with diverse NSCLC subtypes; #3 (Yale, n=138) with molecularly annotated lung adenocarcinomas (ADC); and #4 (Yale, n=46) with patient-matched NSCLC and morphologically-normal lung tissue. We examined associations between marker levels, myeloid cell profiles, clinicopathologic/molecular variables and survival.Results The levels of CD68+ M1 like macrophages were significantly lower and the fraction of CD11b+/HLA-DR− MDSC-like cells was prominently higher in tumor than in matched non-tumor lung tissues. HLA-DR was consistently higher in myeloid cells from tumors with elevated CD68 expression. Stromal CD11b was significantly higher in squamous cell carcinomas (SCC) than in ADC across the cohorts and EGFR-mutated lung ADCs displayed lower CD11b levels than KRAS-mutant tumors. Increased stromal CD68- and HLA-DR-expressing cells was associated with better survival in ADCs from two independent NSCLC cohorts. In SCC, increased stromal CD11b or HLA-DR expression was associated with a trend towards shorter 5-year survival.Conclusions NSCLCs display an unfavorable myeloid immune contexture relative to non-tumor lung and exhibit distinct myeloid-cell profiles across histologies and presence of major oncogenic driver-mutations. Elevated M1-like stromal proinflammatory myeloid cells are prognostic in lung ADC, but not in SCC.https://jitc.bmj.com/content/10/7/e005025.full |
| spellingShingle | Roy S Herbst Lieping Chen David L Rimm Miguel F Sanmamed Kurt A Schalper Alice Li Konstantinos Syrigos Jovian Yu Adam Aguirre-Ducler Brian S Henick Franz Villarroel-Espindola Ila Datar Shruti Desai Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer Journal for ImmunoTherapy of Cancer |
| title | Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer |
| title_full | Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer |
| title_fullStr | Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer |
| title_full_unstemmed | Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer |
| title_short | Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer |
| title_sort | quantitative tissue analysis and role of myeloid cells in non small cell lung cancer |
| url | https://jitc.bmj.com/content/10/7/e005025.full |
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