Modulation of adaptive immunity by soluble products of head and neck squamous cell carcinoma (HNSCC) cells: a role for tumor-derived galanin?

• Grant number: 14/50312-1
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2014
• End date: August 31, 2016
• Field of knowledge: Health Sciences - Dentistry
• Agreement: University of Michigan
• Principal Investigator: Carlos Rossa Junior
• Grantee: Carlos Rossa Junior
• Principal researcher abroad: Nisha Jacinta da Silva
• Institution abroad: University of Michigan, United States
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 12/24196-9 - Modulation of adaptive immunity by soluble products of HNSCC cells: a role for tumor-derived galanin?, AP.R

Abstract

Squamous cell carcinoma of the head and neck (HNSCC) is a locally invasive cancer with a poor prognosis when diagnosed in advanced stages. Changes in the cytokine profile in the plasma of HNSCC patients suggest a shift of the immune response to a Th2 profile, with reduced interleukin (IL)-12 and increased IL-10 expression as HNSCC progresses from stages 1111 to stages IIII1V. Moreover, the status of adaptive immune response has been related with outcome, as a higher percentage of CD8+ T cells were associated with better response to treatment and increased survival in advanced-stage HNSCC. This information indicates a marked effect of HNSCC on the immune response, however there is a relative paucity of information on tumor-immune response interactions in HNSCC. Galanin, a small peptide originally associated with neuronal cell function, is highly expressed by some HNSCC celllines. This peptide can engage three different receptors (GaIR1, 2 and 3), which have varying levels of expression in HNSCC cells. In rat thymocytes, only GalR1 and GalR3 expression was detected, andstirnulation of these cells with galanin decreased proliferation and increased apoptosis; which in the context of HNSCC cells expressing high levels of galanin may represent an immune evasion mechanism.The role of increased galanin expression by HNSCC cells on T cell response has not been investigated and the main hypothesis for this proposal is: increased expression of galanin by HNSCC cells is crucial on the modulation of adaptive immune response by these tumors. Specific aims: 1. Determine the modulation of adaptive immunity by soluble products derived from HNSCC cells; 2. Verify the role of increased GALR2 signaling in HNSCC cells on the modulation of adaptive immunity and 3. Determine if modulation of immune response by HNSCC confers and advantage for tumor progression. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE MEDEIROS, MARCELL COSTA; BANERJEE, RAJAT; LIU, MIN; ANOVAZZI, GIOVANA; D'SILVA, NISHA J.; ROSSA, JR., CARLOS. HNSCC subverts PBMCs to secrete soluble products that promote tumor cell proliferation. ONCOTARGET, v. 8, n. 37, p. 60860-60874, SEP 5 2017. (14/16436-5, 14/50312-1, 14/06472-4, 12/24196-9)

ROSSA, JR., CARLOS; D'SILVA, NISHA J.. Immune-relevant aspects of murine models of head and neck cancer'. Oncogene, v. 38, n. 21, p. 3973-3988, MAY 23 2019. (14/50312-1, 17/14283-5)