title: PD-L1 expression in basaloid squamous cell lung carcinoma: Relationship to PD-1+and CD8+tumor-infiltrating T cells and outcome.
abstract: PD-1/PD-L1 inhibitors demonstrated durable clinical responses in patients with lung squamous cell carcinoma. However, the expression pattern of PD-L1 and the presence of CD8+and PD-1+tumor-infiltrating T cells in the basaloid variant of squamous cell carcinoma remain unknown. immunohistochemistry analysis of PD-L1 expression, with three recently validated monoclonal antibodies used in clinical trials (clones SP142, SP263, and 28-8), and detection of CD8+and PD-1+tumor-infiltrating T cells was performed on whole-tissue sections from 56 patients following surgery for basaloid squamous cell carcinoma. Data were correlated to clinicopathological parameters and outcome. Fair to poor concordance was observed between the SP142 vs SP263 clones, and SP142 vs 28-8 (κ range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (κ=0.883, and κ=0.721). Expression of PD-L1 correlated with a high content of CD8+and PD-1+tumor-infiltrating T cells when using SP142 (P=0.012; P=0.022), but not with SP263 or 28-8 (P=0.314; P=0.611). In the multivariate analysis, we found significantly better disease-free and overall survival rates for high PD-L1 expression with SP142, CD8+and PD-1+tumor-infiltrating T cells (P=0.003; P=0.007). No significant prognosis value was observed for SP263 and 28-8 clones, except a correlation between improved overall survival and SP263 in the univariate analysis (P=0.039), not confirmed in the multivariate model. In conclusion, we report that the expression of PD-L1 and the content of CD8+and PD-1+tumor-infiltrating T cells is an independent indicator of better outcome in basaloid squamous cell carcinoma patients, although the observed effect is dependent on the PD-L1 immunohistochemistry assay.
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.|Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.|Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France.|University Hospital Federation (FHU) OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France.
authors: Marius
authors: 0000-0002-2014-1236
authors: M
authors: Ilie
authors: Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.|Department of Radiation Oncology, Antoine Lacassagne Cancer Center, Nice, France.
authors: Alexander T
authors: AT
authors: Falk
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Catherine
authors: C
authors: Butori
authors: Biostatistics Unit, Antoine Lacassagne Cancer Center, Nice, France.
authors: Emmanuel
authors: E
authors: Chamorey
authors: Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.
authors: Christelle
authors: C
authors: Bonnetaud
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Elodie
authors: E
authors: Long
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Sandra
authors: S
authors: Lassalle
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors: Katia
authors: K
authors: Zahaf
authors: Department of Thoracic Surgery, Pasteur Hospital, Nice, France.
authors: Nicolas
authors: N
authors: Vénissac
authors: Department of Thoracic Surgery, Pasteur Hospital, Nice, France.
authors: Jérôme
authors: J
authors: Mouroux
authors: Department of Thoracic Surgery, Pasteur Hospital, Nice, France.
authors: Charlotte
authors: C
authors: Cohen
authors: Department of Pathology, CHU Albert Michallon, INSERM U823, Université Grenoble Alpes, Grenoble, France.
authors: Elisabeth
authors: E
authors: Brambilla
authors: Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.|University Hospital Federation (FHU) OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France.|Department of Pneumology, Pasteur Hospital, Nice, France.
authors: Charles Hugo
authors: CH
authors: Marquette
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.|Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.|Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France.|University Hospital Federation (FHU) OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France.
authors: Véronique
authors: V
authors: Hofman
authors: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.|Institute for Research on Cancer and Ageing, Nice (IRCAN), INSERM U1081/UMR CNRS 7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Center, Nice, France.|Hospital-Integrated Biobank BB-0033-00025, Pasteur Hospital, Nice, France.|University Hospital Federation (FHU) OncoAge, CHU de Nice, University of Nice Sophia Antipolis, Nice, France.
authors: Paul
authors: P
authors: Hofman
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human