PD-L1 Expression is Increased in Metastasizing Squamous Cell Carcinomas and Their Metastases

Abstract

Programmed cell death ligand 1 (PD-L1) expression by tumor cells plays an important role in the inhibition of T cell-mediated immune response in cancer. PD-L1 expression by tumor cells has been linked to poor prognosis in a wide variety of cancers. However, PD-L1 expression in cutaneous squamous cell carcinoma (cSCC) has been scarcely studied, and its role as a prognosis biomarker remains controversial. The association of PD-L1 expression and the metastatic risk in a series of cSCC was assessed. PD-L1 and CD8 immunostainings of full excision sections of 99 primary tumors and 24 lymphatic metastases were semiquantitatively evaluated. Primary cSCCs were grouped according to the development of lymphatic metastatic spread [metastasizing squamous cell carcinoma (MSCC)] (n = 48) or the absence of progression [nonmetastasizing squamous cell carcinoma (NMSCC)] (n = 51). PD-L1-positive expression (cut off ≥1%) was found in 26% NMSCCs and in 50% MSCCs (P = 0.02). PD-L1 association with an increased metastatic risk was confirmed in the multivariate analysis (P < 0.05), along with the following features: recurrence, poor differentiation, and perineural invasion. Ninety percent of the metastases of PD-L1-positive tumors were also positive for PD-L1, displaying a trend toward a higher PD-L1 expression when compared with their primary tumors (P = 0.058). No significant differences in the peritumoral inflammatory infiltrate or in the expression of CD8 were found between metastasizing and nonmetastasizing primary tumors. Our results suggest that PD-L1 may play a relevant role in metastatic spread and may be a candidate prognostic biomarker in cSCC.

Differential expression of programmed death‐1 according to the histological differentiation of cutaneous squamous cell carcinoma

“…However, we could not find any significant difference in the proportion of PD‐L1 immunoreactivity according to the degree of cSCC differentiation. Although PD‐L1 expression is reported to be strongly associated with nodal metastasis of cSCC, previous studies had differing results, one with a positive correlation with higher histological grade of cSCC, the other not . In conclusion, our results suggest that PD‐1 can be a differential biological marker of well‐differentiated cSCC.…”

“…Unlike its oncogenic functions in melanoma, blockade of PD‐1 promoted tumour cell proliferation in nonsmall cell lung cancer . Studies on the expression of PD‐L1 in cutaneous squamous cell carcinoma (cSCC) have increased . Expression of PD‐1 has also been studied in cSCC …”

European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention

“…Microenvironment is implicated in cSCC, with a role for human leukocyte antigen (HLA) variants [82] and the programmed cell death protein 1/programmed cell death ligand-1 (PD-1/PD-L1) axis. PD-L1 expression was detected in around 26% of primary cSCC [83e85] and up to 50% of metastatic lesions [84,85] Hereditary syndromes that increase cSCC risk include xeroderma pigmentosum, epidermolysis bullosa, oculocutaneous albinism and Fanconi anaemia and Lynch syndrome/Muir Torre syndrome [7].…”

Cutaneous Squamous Cell Carcinoma: From Biology to Therapy

“…These preliminary results justified closer examination of this pathway and its potential therapeutic role in CSCC. Some studies demonstrated the presence of cell surface PD-1/PD-L1 in human tumors, and this expression has been linked to poor clinical outcomes in a variety of cancers [112][113][114][115][116], including CSCC [117,118]. CSCC has the highest mutational burden of all tumors, and is a good candidate for immunotherapy treatment [21].…”