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: Marius Ilie, Alexander T Falk, Catherine Butori, Emmanuel Chamorey, Christelle Bonnetaud, Elodie Long, Sandra Lassalle, Katia Zahaf, Nicolas Vénissac, Jérôme Mouroux, Charlotte Cohen, Elisabeth Brambilla, Charles Hugo Marquette, Véronique Hofman, Paul Hofman
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 29 Issue 12 Pg. 1552-1564 (12 2016) ISSN: 1530-0285 [Electronic] United States
• PMID: 27562497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• B7-H1 Antigen
• Biomarkers, Tumor
• CD274 protein, human

Topics

• Adult
• Aged
• B7-H1 Antigen (analysis, biosynthesis)
• Biomarkers, Tumor (analysis)
• CD8-Positive T-Lymphocytes (immunology)
• Carcinoma, Squamous Cell (immunology, metabolism, mortality)
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (immunology, metabolism, mortality)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Middle Aged
• Prognosis
• Proportional Hazards Models
• Retrospective Studies