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Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer.
Henick, Brian S; Villarroel-Espindola, Franz; Datar, Ila; Sanmamed, Miguel F; Yu, Jovian; Desai, Shruti; Li, Alice; Aguirre-Ducler, Adam; Syrigos, Konstantinos; Rimm, David L; Chen, Lieping; Herbst, Roy S; Schalper, Kurt A.
Afiliação
  • Henick BS; Medicine, Columbia University Irving Medical Center, New York, New York, USA.
  • Villarroel-Espindola F; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
  • Datar I; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
  • Sanmamed MF; Yale Cancer Center, New Haven, Connecticut, USA.
  • Yu J; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
  • Desai S; Yale Cancer Center, New Haven, Connecticut, USA.
  • Li A; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
  • Aguirre-Ducler A; Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
  • Syrigos K; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
  • Rimm DL; Sotiria General Hospital, National and Kapodistrian University of Athens, Athens, Athens, Greece.
  • Chen L; Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
  • Herbst RS; Yale Cancer Center, New Haven, Connecticut, USA.
  • Schalper KA; Yale Cancer Center, New Haven, Connecticut, USA.
J Immunother Cancer ; 10(7)2022 07.
Article em En | MEDLINE | ID: mdl-35793873
ABSTRACT

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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Escamosas / Carcinoma Pulmonar de Células não Pequenas / Adenocarcinoma de Pulmão / Neoplasias Pulmonares Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Carcinoma de Células Escamosas / Carcinoma Pulmonar de Células não Pequenas / Adenocarcinoma de Pulmão / Neoplasias Pulmonares Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article