MORÓN VÍCTOR GABRIEL
Congresos y reuniones científicas
Título:
IMPAIRED ANTITUMOR IMMUNITY IN LSP1-/- MICE IS ACCOMPANIED BY AN INTRATUMORAL CYTOKINE DISBALANCE
Autor/es:
MERCEDES PASCUAL; NICOLAS DANIEL DHO; MARÍA INÉS CRESPO; MARÍA C PISTORESI- PALENCIA; BELKYS A. MALETTO; G MORON
Lugar:
virtual
Reunión:
Congreso; LXIX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2021
Institución organizadora:
SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI)
Resumen:
Leukocyte-specific protein 1 (LSP1) is a 52kDa cytoplasmic F-actin
binding phosphoprotein expressed in all human and murine leukocytes as well as in endothelial cells. This protein in known as an
important regulator of actin cytoskeleton remodeling. LSP1 polymorphisms
or downregulation are considered risk factors for some types
of cancer.
We previously shown that B16-OVA melanoma in Lsp1-/- mice grows
significantly faster and bigger than in wild type (WT) controls. Also,
tumors harvested from Lsp1-/- mice show a lower frequency of total
infiltrating leukocytes compared to WT mice. Furthermore, there is
a reduced extravasation efficiency of Lsp1-/- leukocytes into tumor,
combined with a defective CD8+ T cell priming in Lsp1-/- tumor dLN.
We continued this study by comparing the cytokine milieu in melanoma
tumors in Lsp1-/- vs WT mice. For that, 1.105 B16-OVA melanoma
cells were implanted in both animal groups and on day 16 tumors
were harvested. Aproximately 70 mg tumor/mouse was digested
using T-PER? Tissue Protein Extraction Reagent added with protease
inhibitor. Tumor-cytokine content was determined by a multiplex
commercial assay using fluorescence?encoded beads that allows
simultaneous quantification of 13 mouse cytokines including IL-1α,
IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β,
IFN-γ, TNF-α and GM-CSF. We found that tumors in Lsp1-/- mice
have significantly higher levels of IL-1β, IL-10, IL-27, IL-17A and IL-
23 (p<0.01) as well as higher levels of TNF-α, IL-12p70, IFN-β and
GM-CSF (p<0.001) than WT mice. However, tumor extracts contained
similar levels of IL-1α, INF-γ, MCP-1 and IL-6. Sumarizing,
the tumoral milieu in Lsp1-/- mice has increased levels of cytokines
that can act as angiogenesis promoters, favoring tumoral growth
and chronic inflammation, as well as cytokines involved in promoting
DC activation.
binding phosphoprotein expressed in all human and murine leukocytes as well as in endothelial cells. This protein in known as an
important regulator of actin cytoskeleton remodeling. LSP1 polymorphisms
or downregulation are considered risk factors for some types
of cancer.
We previously shown that B16-OVA melanoma in Lsp1-/- mice grows
significantly faster and bigger than in wild type (WT) controls. Also,
tumors harvested from Lsp1-/- mice show a lower frequency of total
infiltrating leukocytes compared to WT mice. Furthermore, there is
a reduced extravasation efficiency of Lsp1-/- leukocytes into tumor,
combined with a defective CD8+ T cell priming in Lsp1-/- tumor dLN.
We continued this study by comparing the cytokine milieu in melanoma
tumors in Lsp1-/- vs WT mice. For that, 1.105 B16-OVA melanoma
cells were implanted in both animal groups and on day 16 tumors
were harvested. Aproximately 70 mg tumor/mouse was digested
using T-PER? Tissue Protein Extraction Reagent added with protease
inhibitor. Tumor-cytokine content was determined by a multiplex
commercial assay using fluorescence?encoded beads that allows
simultaneous quantification of 13 mouse cytokines including IL-1α,
IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β,
IFN-γ, TNF-α and GM-CSF. We found that tumors in Lsp1-/- mice
have significantly higher levels of IL-1β, IL-10, IL-27, IL-17A and IL-
23 (p<0.01) as well as higher levels of TNF-α, IL-12p70, IFN-β and
GM-CSF (p<0.001) than WT mice. However, tumor extracts contained
similar levels of IL-1α, INF-γ, MCP-1 and IL-6. Sumarizing,
the tumoral milieu in Lsp1-/- mice has increased levels of cytokines
that can act as angiogenesis promoters, favoring tumoral growth
and chronic inflammation, as well as cytokines involved in promoting
DC activation.
