Targeting the polarization of tumor-associated macrophages and modulating mir-155 expression might be a new approach to treat diffuse large B-cell lymphoma of the elderly.

Autor: Poles WA; Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, Rua Diogo de Faria, 824, 5° andar, Hemocentro, CEP 04037-002, Sao Paulo, Brazil., Nishi EE; Department of Physiology, Universidade Federal de São Paulo, Sao Paulo, Brazil., de Oliveira MB; Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, Rua Diogo de Faria, 824, 5° andar, Hemocentro, CEP 04037-002, Sao Paulo, Brazil., Eugênio AIP; Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, Rua Diogo de Faria, 824, 5° andar, Hemocentro, CEP 04037-002, Sao Paulo, Brazil., de Andrade TA; Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, Rua Diogo de Faria, 824, 5° andar, Hemocentro, CEP 04037-002, Sao Paulo, Brazil., Campos AHFM; Department of Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil., de Campos RR Jr; Department of Physiology, Universidade Federal de São Paulo, Sao Paulo, Brazil., Vassallo J; Department of Pathology, AC Camargo Cancer Center, Sao Paulo, Brazil., Alves AC; Department of Pathology, Universidade Federal de São Paulo, Sao Paulo, Brazil., Scapulatempo Neto C; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Paes RAP; Faculty of Medical Sciences of Santa Casa of São Paulo, Sao Paulo, Brazil., Landman G; Department of Pathology, Universidade Federal de São Paulo, Sao Paulo, Brazil., Zerbini MCN; Department of Pathology, Universidade de São Paulo, Sao Paulo, Brazil., Colleoni GWB; Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, Rua Diogo de Faria, 824, 5° andar, Hemocentro, CEP 04037-002, Sao Paulo, Brazil. gcolleoni@unifesp.br.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2019 Feb; Vol. 68 (2), pp. 269-282. Date of Electronic Publication: 2018 Nov 14.
DOI: 10.1007/s00262-018-2273-2
Abstrakt: Aging immune deterioration and Epstein-Barr (EBV) intrinsic mechanisms play an essential role in EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV + DLBCLe) pathogenesis, through the expression of viral proteins, interaction with host molecules and epigenetic regulation, such as miR-155, required for induction of M1 phenotype of macrophages. This study aims to evaluate the relationship between macrophage polarization pattern in the tumor microenvironment and relative expression of miR-155 in EBV + DLBCLe and EBV-negative DLBCL patients. We studied 28 EBV + DLBCLe and 65 EBV-negative DLBCL patients. Tumor-associated macrophages (TAM) were evaluated by expression of CD68, CD163 and CD163/CD68 ratio (degree of M2 polarization), using tissue microarray. RNA was extracted from paraffin-embedded tumor samples for miR-155 relative expression study. We found a significantly higher CD163/CD68 ratio in EBV + DLBCLe compared to EBV-negative DLBCL. In EBV-negative DLBCL, CD163/CD68 ratio was higher among advanced-staged/high-tumor burden disease and overexpression of miR-155 was associated with decreased polarization to the M2 phenotype of macrophages. The opposite was observed in EBV + DLBCLe patients: we found a positive association between miR-155 relative expression and CD163/CD68 ratio, which was not significant after outlier exclusion. We believe that the higher CD163/CD68 ratio in this group is probably due to the presence of the EBV since it directly affects macrophage polarization towards M2 phenotype through cytokine secretion in the tumor microenvironment. Therapeutic strategies modulating miR-155 expression or preventing immuno-regulatory and pro-tumor macrophage polarization could be adjuvants in EBV + DLBCLe therapy since this entity has a rich infiltration of M2 macrophages in its tumor microenvironment.
Databáze: MEDLINE
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