MORÓN VÍCTOR GABRIEL
Congresos y reuniones científicas
Título:
REDUCED EXTRAVASATION EFFICIENCY OF LSP1- /- LEUKOCYTES COMBINED WITH A DEFECTIVE CD8+ T CELLS PRIMING IN LSP1-/- TUMOR DRAINING LYMPH NODE CAUSED AN IMPAIRED ANTITUMOR IMMUNITY RESPONSE IN LSP1-/- MICE
Autor/es:
MERCEDES PASCUAL; NICOLAS DANIEL DHO; MARÍA INÉS CRESPO; MARÍA C PISTORESI- PALENCIA; BELKYS A. MALETTO; G MORON
Lugar:
Buenos Aires
Reunión:
Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2020
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.
In order to study the role of LSP1 in antitumor immune response, we
employed the B16-OVA melanoma model.
We previously shown that B16-OVA tumor in Lsp1-/- mice grow 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.
Considering that LSP1 is expressed by leukocytes and endothelial
cells, an in vivo migration assay was performed. WT and Lsp1-
/- splenocytes were labeled with Cell Proliferation Dye eFluor 670
(3μM and 0.3μM respectively), mixed in a 1:1 ratio and adoptively
transferred into WT or Lsp1-/- tumor-bearing mice. We observed a
lower frequency of Lsp1-/- migrant leukocytes in tumors developed
in WT and Lsp1-/- mice (p<0.01 and p<0.001 respectively) 48hr after
transfection. However, no difference in migrant cells was found
when tumor draining lymph nodes (dLN) were analyzed.
Taking into account CD8+ T cells priming importance in antitumor
immunity, an in vivo proliferation assay was performed, by transferring
CD8+ T cells from OT I mice to WT and Lsp1-/- tumor-bearing
mice. Transferred CD8+ T cells failed to proliferate in Lsp1-/- dLN
compared to WT dLN 48hr after cell transference (p<0.01). Additionally,
we observed that transferred CD8+ T cells in Lsp1-/- mice
displayed a significantly lower activation pattern as measured by
expression of CD69 and CD44 (p<0.01).
We hypothesize that the impaired control of melanoma growth in
Lsp1-/- mice could be caused, by a reduced extravasation efficiency
of Lsp1-/- leukocytes, combined with a defective CD8+ T cells priming
in Lsp1-/- tumor dLN.
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.
In order to study the role of LSP1 in antitumor immune response, we
employed the B16-OVA melanoma model.
We previously shown that B16-OVA tumor in Lsp1-/- mice grow 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.
Considering that LSP1 is expressed by leukocytes and endothelial
cells, an in vivo migration assay was performed. WT and Lsp1-
/- splenocytes were labeled with Cell Proliferation Dye eFluor 670
(3μM and 0.3μM respectively), mixed in a 1:1 ratio and adoptively
transferred into WT or Lsp1-/- tumor-bearing mice. We observed a
lower frequency of Lsp1-/- migrant leukocytes in tumors developed
in WT and Lsp1-/- mice (p<0.01 and p<0.001 respectively) 48hr after
transfection. However, no difference in migrant cells was found
when tumor draining lymph nodes (dLN) were analyzed.
Taking into account CD8+ T cells priming importance in antitumor
immunity, an in vivo proliferation assay was performed, by transferring
CD8+ T cells from OT I mice to WT and Lsp1-/- tumor-bearing
mice. Transferred CD8+ T cells failed to proliferate in Lsp1-/- dLN
compared to WT dLN 48hr after cell transference (p<0.01). Additionally,
we observed that transferred CD8+ T cells in Lsp1-/- mice
displayed a significantly lower activation pattern as measured by
expression of CD69 and CD44 (p<0.01).
We hypothesize that the impaired control of melanoma growth in
Lsp1-/- mice could be caused, by a reduced extravasation efficiency
of Lsp1-/- leukocytes, combined with a defective CD8+ T cells priming
in Lsp1-/- tumor dLN.
