HNSCC subverts PBMCs to secrete soluble products that promote tumor cell proliferation

Autor(es)

de Medeiros, Marcell Costa ; Banerjee, Rajat ; Liu, Min ; Anovazzi, Giovana ; D'Silva, Nisha J. ; Rossa, Jr., Carlos

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 8, n. 37, p. 60860-60874, SEP 5 2017.
• Citações Web of Science: 2

Resumo

The immune system detects shifts from homeostasis and eliminates altered cells. However, neoplastic cells can modulate the host response to escape immunosurveillance thereby allowing tumor progression. Head and neck squamous cell carcinoma (HNSCC) is one of the most immunosuppressive cancers but its role in co-opting the immune system to actively promote tumor growth has not been investigated. In this study, we investigated the influence of soluble factors secreted by HNSCC and non-neoplastic epithelial cells on proliferation, apoptosis, activation, cytokine gene expression and phenotypic polarization of immune cells of healthy donors. Then, we determined if the immunomodulation caused by HNSCC-derived soluble products leads to immunosubversion by assessing proliferation, migration and survival of tumor cells exposed to soluble products secreted by modulated immune cells or co-cultured with immune cells. Soluble products from HNSCC inhibited proliferation and cytokine expression in PBMCs, activation of T cells, and polarization of CD4+ towards the Th17 phenotype. These changes co-opted the immune cells to favor cell proliferation, survival and migration of HNSCC. This immunosubversion was observed both indirectly with secreted products and with direct cell-to-cell contact. We conclude that HNSCC-derived secreted products create an immunosuppressive environment that facilitates evasion of tumor cells and subverts the immune cells into a pro-tumoral phenotype. (AU)

• Processo FAPESP: 14/06472-4 - Modulação da imunidade adaptativa por produtos solúveis de células de HNSCC: um papel da galanina derivada do tumor?
• Beneficiário: Marcell Costa de Medeiros
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/16436-5 - Modulação da imunidade adaptativa por produtos solúveis de células de HNSCC: um papel da galanina derivada do tumor?
• Beneficiário: Marcell Costa de Medeiros
• Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 14/50312-1 - Modulação da imunidade adaptativa por produtos solúveis de carcinoma espinocelular de cabeça e pescoço (HNSCC): um papel da galanina derivada do tumor?
• Beneficiário: Carlos Rossa Junior
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/24196-9 - Modulação da imunidade adaptativa por produtos solúveis de células de HNSCC: um papel da galanina derivada do tumor?
• Beneficiário: Carlos Rossa Junior
• Linha de fomento: Auxílio à Pesquisa - Regular