Reduced Interleukin-17-Expressing Cells in Cutaneous Melanoma.

Anna Tosi,Francesca Passarelli,Cristina Maria Failla,Cristina Fortes,Lorena Capriotti,Fernanda Scopelliti,Andrea Cavani,Caterina Cattani,Simona Mastroeni,Lavinia Nardinocchi,Antonio Rosato,Maria Luigia Carbone,Stefania D’Atri,Elena Pagani

doi:10.3390/biomedicines9121930

Abstract

Characterization of tumor associated lymphocytes (TILs) in tumor lesions is important to obtain a clear definition of their prognostic value and address novel therapeutic opportunities. In this work, we examined the presence of T helper (Th)17 lymphocytes in cutaneous melanoma. We performed an immunohistochemical analysis of a small cohort of primary melanomas, retrospectively selected. Thereafter, we isolated TILs from seven freshly surgically removed melanomas and from three basal cell carcinomas (BCC), as a comparison with a non-melanoma skin cancer known to retain a high amount of Th17 cells. In both studies, we found that, differently from BCC, melanoma samples showed a lower percentage of Th17 lymphocytes. Additionally, TIL clones could not be induced to differentiate towards the Th17 phenotype in vitro. The presence or absence of Th17 cells did not correlate with any patient characteristics. We only observed a lower amount of Th17 cells in samples from woman donors. We found a tendency towards an association between expression by melanoma cells of placenta growth factor, angiogenic factors able to induce Th17 differentiation, and presence of Th17 lymphocytes. Taken together, our data indicate the necessity of a deeper analysis of Th17 lymphocytes in cutaneous melanoma before correlating them with prognosis or proposing Th17-cell based therapeutic approaches.

Highlights

Compared with that of the peripheral blood mononuclear cells (PBMC) from the same patient or with that of tumor associated lymphocytes (TILs) isolated from basal cell carcinomas (BCC). * p < 0.05; Student’s the PBMCs from the same patient or with that of TILs isolated from BCCs. * p < 0.05; Student’s ttest
This result was unexpected, as Th17 lymphocytes were previously detected in other human tumor tissues, such as ovarian, pancreatic, and renal cell carcinoma, as well as in a mouse model of melanoma [37] and in some human melanoma cell lines [24]
There is the possibility that human melanoma expresses a combination of factors able to restrict T cell differentiation towards the Th17 phenotype or inhibit Th17 recruitment at the tumor site

Summary

Introduction

Licensee MDPI, Basel, Switzerland.Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).The presence of an inflammatory infiltrate of both innate and adaptive immune cells around the tumor has been long recognized and can be interpreted in different ways [1]. It may reflect a protective host response against cancer cells or a persistent tumor-promoted inflammation able to foster fibrosis, angiogenesis, and tumor progression [2].In cutaneous melanoma, tumor-infiltrating lymphocytes (TILs) can be present focally or diffusively at the tumor periphery and histological samples can be categorized based on TIL density and distribution pattern [3,4]. In the majority of epidemiological studies, the Biomedicines 2021, 9, 1930. https://doi.org/10.3390/biomedicines9121930 https://www.mdpi.com/journal/biomedicines

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Conclusion