4.6 Article

PD-L1 expression in basaloid squamous cell lung carcinoma: Relationship to PD-1+ and CD8+ tumor-infiltrating T cells and outcome

Journal

MODERN PATHOLOGY
Volume 29, Issue 12, Pages 1552-1564

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1038/modpathol.2016.149

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Funding

  1. Fondation ARC pour la recherche sur le cancer [ARC SL220110603478]
  2. Boehringer-Ingelheim France
  3. French National Cancer Institute (INCa)

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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 (kappa range, 0.018-0.412), while the 28-8 and SP263 demonstrated a strong correlation in both the tumor cell and immune cell compartments (kappa = 0.883, and kappa=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.

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