Research Papers: Immunology:

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

Marcell Costa de Medeiros _, Rajat Banerjee, Min Liu, Giovana Anovazzi, Nisha J. D’Silva and Carlos Rossa Junior

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Oncotarget. 2017; 8:60860-60874. https://doi.org/10.18632/oncotarget.18486

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Marcell Costa de Medeiros1, Rajat Banerjee2, Min Liu2, Giovana Anovazzi1, Nisha J. D’Silva2,3 and Carlos Rossa Junior1

1 Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University, Araraquara, SP, Brazil

2 Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA

3 Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA

Correspondence to:

Carlos Rossa Junior, email:

Nisha J. D’Silva, email:

Keywords: head and neck squamous cell carcinoma, immune response, T cell, immunosuppression and tumor scape, Immunology and Microbiology Section, Immune response, Immunity

Received: January 12, 2017 Accepted: June 01, 2017 Published: June 15, 2017


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.

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