Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1) and strong immune-cell infiltration by TCD3 cells and macrophages.
Lung Cancer
; 98: 51-58, 2016 08.
Article
in En
| MEDLINE
| ID: mdl-27393506
ABSTRACT
OBJECTIVES:
Pulmonary sarcomatoid carcinomas (SC) are rare tumors, associated with worse prognosis and resistant to platinum-based regimens. Therapies targeting the PD-1/PD-L1 pathway are an emerging treatment for lung cancer. By characterizing intra-tumoral immune infiltration and evaluating PD-L1 expression, it could be possible to predict the efficacy of these new treatments. MATERIALS ANDMETHODS:
From 1997 to 2013, data from all patients with SC who underwent lung resection was collected. Tumor-immune infiltration and PD-L1 expression were studied by immunochemistry tests, analyzing CD3 (clone SP7), CD4 (clone 1F6), CD8 (clone C8/144b), CD20 (clone L26), CD163 (clone 10D6), MPO (clone 59A5), and PD-L1 (clone 5H1). Results were compared to those of 54 NSCLC.RESULTS:
In total, 75 SC were included. Forty (53%) SC expressed PD-L1 vs 11 NSCLC (20%) (p<0.0001). CD3+ tumor-infiltrating lymphocytes and CD163+ tumor-associated macrophages were more important in SC than in NSCLC (median 23% [17-30] of tumoral surface vs 17% [7-27], p=0.011 and 23% [17-30] vs 20% [13-23], p=0.002, respectively). In SC, the presence of Kirsten Ras (KRAS) mutations, blood vessel invasion, and TTF1+ positivity were associated with PDL1 expression. On multivariate analysis, only CD163+ macrophages and blood-vessel invasion were associated with tumoral PD-L1 expression. High levels of tumor-infiltrating lymphocytes (CD3+ or CD4+ and not CD8+) constituted a factor of good prognosis on survival. Interestingly, PD-L1 expression distinguishes subpopulations within tumor-infiltrating lymphocytes (CD3+ or CD4+) with different prognosisCONCLUSIONS:
PD-L1 expression was higher in SC than in NSCLC as well as immune-cell infiltration by TCD3 cells and macrophages. This suggests that targeting the PD-1/PD-L1 pathway could represent a new potential therapy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocytes, Tumor-Infiltrating
/
B7-H1 Antigen
/
Lung Neoplasms
/
Macrophages
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Lung Cancer
Journal subject:
NEOPLASIAS
Year:
2016
Document type:
Article
Affiliation country:
France