Quantitative, Spatially Defined Expression of Leukocyte-associated Immunoglobulin-like Receptor in Non-small Cell Lung Cancer.
| Autor: | Aung TN; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Gavrielatou N; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.; Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Vathiotis IA; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.; Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Fernandez AI; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Shafi S; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Yaghoobi V; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Burela S; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., MacNeil T; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Ahmed FS; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Myint H; NextCure Inc, Beltsville, Maryland., Flies DB; NextCure Inc, Beltsville, Maryland., Langermann S; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut., Rimm DL; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.; Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Cancer research communications [Cancer Res Commun] 2023 Mar 21; Vol. 3 (3), pp. 471-482. Date of Electronic Publication: 2023 Mar 21 (Print Publication: 2023). |
| DOI: | 10.1158/2767-9764.CRC-22-0334 |
| Abstrakt: | Targeting the interaction of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) and its ligands has been shown to reinstate antitumor immunity. In addition, the introduction of the LAIR-1 decoy protein, LAIR-2, sensitizes previously resistant lung tumors to programmed death-1 (PD-1) blockade, indicating the potential of LAIR-1 as an alternative marker for anti-PD-1 resistance in lung cancer. Here, we assessed LAIR-1 as compared with programmed death-ligand 1 (PD-L1) expression in various tumors, with a focus on non-small cell lung cancer (NSCLC) and its histologic subtypes using multiplexed quantitative immunofluorescence (mQIF) in 287 (discovery cohort) and 144 (validation cohort) patients with NSCLC. In addition, using multispectral imaging technology on mQIF images, we evaluated the localization of LAIR-1 on various cell types. We observed that CD14 + , CD68 + , and CD163 + monocytes and CK + tumor cells predominantly expressed LAIR-1 more than other cell types. Furthermore, LAIR-1 expression in the tumor compartment was significantly higher in patients with lung adenocarcinoma (LUAD) than those with lung squamous cell carcinoma subtype (**, P = 0.003). Our results indicated that high tumor LAIR-1 expression in patients with LUAD is negatively associated with OS (overall survival, HR = 2.4; *, P = 0.02) highlighting its prognostic value in LUAD but not in other subtypes. The Pearson correlation between LAIR-1 and PD-L1 is 0.31; however, mutual exclusive staining pattern (i.e., several cases were positive for LAIR-1 and negative for PD-L1) was observed. Altogether, our data suggest that the combination therapy of anti-PD-1/PD-L1 with anti-LAIR-1 or the anti-LAIR-1 monotherapy alone may be promising cancer immunotherapeutic strategies. Significance: The spatial, quantitative assessment of LAIR-1 in NSCLC shows positive association of OS with high LAIR-1 + /CD68 + cell densities and negative association of OS with high LAIR-1 expression in LUAD tumor subtype. (© 2023 The Authors; Published by the American Association for Cancer Research.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|