title: Sarcomatoid lung carcinomas show high levels of programmed death ligand-1 (PD-L1) and strong immune-cell infiltration by TCD3 cells and macrophages.
abstract: 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.
  
  
  
  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.
  
  
  
  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 prognosis
  
  
  
  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.
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France.
authors.forename: Thibault
authors.initials: T
authors.lastname: Vieira
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service d'anatomopathologie, F-75970 Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Antoine
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Hamard
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fallet
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Duruisseaux
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rabbe
authors.affiliation: AP-HP, Hôpital Tenon, service d'anatomopathologie, F-75970 Paris, France.
authors.forename: Anita
authors.initials: A
authors.lastname: Rodenas
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, GRC n°04, Theranoscan, F-75252 Paris, France; AP-HP, Hôpital Tenon, service de Pneumologie, F-75970 Paris, France. Electronic address: marie.wislez@tnn.aphp.fr.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: Lung sarcomatoid carcinoma; Non-small-cell lung cancer; PD-L1; Tumor-Infiltrating lymphocytes; Tumor-Infiltratingmacrophages