Effect of autophagy blockade on the immunogenicity of SW620 colorectal cancer cells

• Grant number: 17/25378-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): May 01, 2018
• Effective date (End): December 31, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ramon Kaneno
• Grantee: Bruna Sanrromão Henrique
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Cancer is featured by an uncontrolled cell proliferation that change the tissue homeostasis and can trigger complications such as pathways blockade, organ compression, and spreading of transformed cells through metastasis. Colorectal cancer is the third main type of cancer worldwide and the most common treatment strategy is chemotherapy, being 5-fluorouracil (5-FU) one of the main drugs used in this disease. One of the problems of chemotherapy, mainly under administration of maximus tolerable dose (MTD) is the selection of resistant cells, facilitating the relapsing diseases and metastasis. One of the mechanisms involved in the development of chemoresistance is authophagy, a process featured by cytoplasm recycling, organelles, and damaged proteins to provide energy and nutrients as well as correct damages in order to keep cell viability. We previously observed that exposition of tumor cells to low concentrations of chemotherapeutic agents induces transcriptional changes that increases the immunogenicity of these cells. Since authophagy takes part of the degradative pathway of intracellular proteins, we hypothesized that it pharmacological blockade could favor the permanence of tumor antigens in the citosol, allowing their processing by the citosolic pathway and subsequent exposition on the cell surface. Aiming to test this hypothesis, colon cancer cells SW620 will be treated with 5-FU to increase their immunogenicity and authophagy will be blockade with hydroxychloroquine. Then, we will evaluate the induction of apoptosis and cell death, the cell cycle and the expression of surface markers.