PMID- 31827382 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20200601 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2019 DP - 2019 TI - Could Increased Expression of Hsp27, an "Anti-Inflammatory" Chaperone, Contribute to the Monocyte-Derived Dendritic Cell Bias towards Tolerance Induction in Breast Cancer Patients? PG - 8346930 LID - 10.1155/2019/8346930 [doi] LID - 8346930 AB - Dendritic cells (DCs) are the most efficient antigen-presenting cells and link the innate immune sensing of the environment to the initiation of adaptive immune responses, which may be directed to either acceptance or elimination of the recognized antigen. In cancer patients, though DCs would be expected to present tumor antigens to T lymphocytes and induce tumor-eliminating responses, this is frequently not the case. The complex tumor microenvironment subverts the immune response, blocks some effector mechanisms, and drives others to support tumor growth. Chronic inflammation in a tumor microenvironment is believed to contribute to the induction of such regulatory/tolerogenic response. Among the various mediators of the modulatory switch in chronic inflammation is the "antidanger signal" chaperone, heat shock protein 27 (Hsp27), that has been described, interestingly, to be associated with cell migration and drug resistance of breast cancer cells. Thus, here, we investigated the expression of Hsp27 during the differentiation of monocyte-derived DCs (Mo-DCs) from healthy donors and breast cancer patients and evaluated their surface phenotype, cytokine secretion pattern, and lymphostimulatory activity. Surface phenotype and lymphocyte proliferation were evaluated by flow cytometry, interferon- (IFN-) gamma, and interleukin- (IL-) 10 secretion, by ELISA and Hsp27 expression, by quantitative polymerase chain reaction (qPCR). Mo-DCs from cancer patients presented decreased expression of DC maturation markers, decreased ability to induce allogeneic lymphocyte proliferation, and increased IL-10 secretion. In coculture with breast cancer cell lines, healthy donors' Mo-DCs showed phenotype changes similar to those found in patients' cells. Interestingly, patients' monocytes expressed less GM-CSF and IL-4 receptors than healthy donors' monocytes and Hsp27 expression was significantly higher in patients' Mo-DCs (and in tumor samples). Both phenomena could contribute to the phenotypic bias of breast cancer patients' Mo-DCs and might prove potential targets for the development of new immunotherapeutic approaches for breast cancer. CI - Copyright (c) 2019 Ana Paula Silva de Azevedo-Santos et al. FAU - de Azevedo-Santos, Ana Paula Silva AU - de Azevedo-Santos APS AUID- ORCID: 0000-0002-6404-0103 AD - Biological and Health Sciences Center, Federal University of Maranhao, Avenida dos Portugueses, 1966, Bacanga, Sao Luis, Brazil. FAU - Rocha, Mirtes Castelo Branco AU - Rocha MCB AD - Biological and Health Sciences Center, Federal University of Maranhao, Avenida dos Portugueses, 1966, Bacanga, Sao Luis, Brazil. FAU - Guimaraes, Sulayne Janayna Araujo AU - Guimaraes SJA AD - Biological and Health Sciences Center, Federal University of Maranhao, Avenida dos Portugueses, 1966, Bacanga, Sao Luis, Brazil. FAU - Vale, Andre Alvares Marques AU - Vale AAM AD - Biological and Health Sciences Center, Federal University of Maranhao, Avenida dos Portugueses, 1966, Bacanga, Sao Luis, Brazil. FAU - Laginha, Fabio Martins AU - Laginha FM AD - Perola Byington Hospital, Avenida Brigadeiro Luis Antonio, 683 Sao Paulo, Brazil. FAU - Nascimento, Flavia Raquel F AU - Nascimento FRF AD - Biological and Health Sciences Center, Federal University of Maranhao, Avenida dos Portugueses, 1966, Bacanga, Sao Luis, Brazil. FAU - Nagai, Maria Aparecida AU - Nagai MA AD - The State of Sao Paulo Cancer Institute (ICESP), Avenida Dr. Arnaldo, 251 Sao Paulo, Brazil. FAU - Bergami-Santos, Patricia C AU - Bergami-Santos PC AD - Institute of Biomedical Sciences, University of Sao Paulo, Avenida Prof. Lineu Prestes, 1730 Sao Paulo, Brazil. FAU - Barbuto, Jose Alexandre Marzagao AU - Barbuto JAM AUID- ORCID: 0000-0001-9526-6781 AD - Institute of Biomedical Sciences, University of Sao Paulo, Avenida Prof. Lineu Prestes, 1730 Sao Paulo, Brazil. LA - eng PT - Journal Article DEP - 20191118 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (HSP27 Heat-Shock Proteins) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Breast Neoplasms/*metabolism MH - Cell Line, Tumor MH - Dendritic Cells/*metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Flow Cytometry MH - HSP27 Heat-Shock Proteins/*metabolism MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Monocytes/*metabolism MH - Polymerase Chain Reaction PMC - PMC6885848 COIS- The authors declare that there is no conflict of interest regarding the publication of this paper. EDAT- 2019/12/13 06:00 MHDA- 2020/06/02 06:00 PMCR- 2019/11/18 CRDT- 2019/12/13 06:00 PHST- 2019/05/17 00:00 [received] PHST- 2019/08/22 00:00 [revised] PHST- 2019/10/01 00:00 [accepted] PHST- 2019/12/13 06:00 [entrez] PHST- 2019/12/13 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2019/11/18 00:00 [pmc-release] AID - 10.1155/2019/8346930 [doi] PST - epublish SO - Mediators Inflamm. 2019 Nov 18;2019:8346930. doi: 10.1155/2019/8346930. eCollection 2019.