Post-Sepsis State Induces Tumor-Associated Macrophage Accumulation through CXCR4/CXCL12 and Favors Tumor Progression in Mice

Author(s):Show less -

Mota, Jose M. ^{[1, 2, 3]} ; Leite, Caio A. ^[1] ; Souza, Lucas E. ^[4] ; Melo, Paulo H. ^[1] ; Nascimento, Daniele C. ^[1] ; de-Deus-Wagatsuma, Virginia M. ^{[5, 2, 3]} ; Temporal, Jessica ^[5] ; Figueiredo, Florencio ^[6] ; Noushmehr, Houtan ^[5] ; Alves-Filho, Jose C. ^[1] ; Cunha, Fernando Q. ^[1] ; Rego, Eduardo M. ^{[2, 3]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Inflammat & Pain, BR-14048900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Hematol Oncol, BR-14048900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Cell Based Therapy, Dept Internal Med, BR-14048900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Lab Gene Sch, BR-14048900 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, OMICS Lab, BR-14048900 Sao Paulo - Brazil

^[6] Univ Brasilia, Dept Pathol, Pathol Lab, Brasilia, DF - Brazil

• Document type: Journal article
• Source: CANCER IMMUNOLOGY RESEARCH; v. 4, n. 4, p. 312-322, APR 2016.
• Web of Science Citations: 11

Abstract

Survivors from sepsis are in an immunosuppressed state that is associated with higher long-term mortality and risk of opportunistic infections. Whether these factors contribute to neoplastic proliferation, however, remains unclear. Tumor-associated macrophages (TAM) can support malignant cell proliferation, survival, and angiogenesis. We addressed the relationship between the post-sepsis state, tumor progression and TAM accumulation, and phenotypic and genetic profile, using a mouse model of sepsis resolution and then B16 melanoma in mice. In addition, we measured the serum concentrations of TNF alpha, TGF beta, CCL2, and CXCL12 and determined the effect of in vivo CXCR4/CXCL12 inhibition in this context. Mice that survived sepsis showed increased tumor progression both in the short and long term, and survival times were shorter. TAM accumulation, TAM local proliferation, and serum concentrations of TGFb, CXCL12, and TNFa were increased. Naive mice inoculated with B16 together with macrophages from post-sepsis mice also had faster tumor progression and shorter survival. Post-sepsis TAMs had less expression of MHC-II and leukocyte activation-related genes. Inhibition of CXCR4/CXCL12 prevented the post-sepsis-induced tumor progression, TAM accumulation, and TAM in situ proliferation. Collectively, our data show that the post-sepsis state was associated with TAM accumulation through CXCR4/CXCL12, which contributed to B16 melanoma progression. (C) 2016 AACR. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/14228-3 - Melanoma B16-F10 in sepsis surviving mice: role of tumor associated macrophages
• Grantee: Eduardo Magalhães Rego
• Support Opportunities: Regular Research Grants