INVESTIGADORES
MAGLIOCO Andrea Florencia
congresos y reuniones científicas
Título:
Characterization of the cells used for adoptive transferene in an immunotherapeutic protocol that induced regression of an established murine tumor
Autor/es:
ANDREA MAGLIOCO; MACHUCA D; MUNDIÑANO J; CABRERA G; CAMICIA G; BADANO N; DRAN G
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Resumen:
Anti-tumor immunity is
often impaired by the growing tumor
by the induction of
immunosuppression and tolerance. Using
an experimental murine
*brosarcoma (MCC) that progresses
from a strongly
immunogenic to a tolerogenic state, we have
previously
demonstrated that MCC growth induces a speci*c
immune response that
coexists with signs of suppression, like
IL-10+ B cells, mainly
at the tumor draining lymph node (TDLN).
We therefore designed
an immunotherapeutic trial consisting of
the ablation of TDLN
in order to eliminate an incipient focus of
suppression, the ex
vivo expansion of the ablated TDLN cytotoxic
cells with
anti-CD3+IL-2, and the re-inoculation of these cells
into the donor
tumor-bearing mouse by adoptive transference.
With this protocol,
lower tumor growth, enhanced survival and
a high rate of
complete tumor remission were obtained. The aim
of the present work
was to characterize the adoptively transferred
cells. Freshly
harvested TDLN cells were mostly composed
of B, CD4+T and CD8+T
cells; ex vivo exposition to anti-CD3+IL-2
increased CD4+ and
CD8+T and decreased B cell proportions (%
cells before versus
after culture: TCD4+: 37±1 vs 74±7***; TCD8+:
17.3±0.5
vs 26.8±6**; B220+CD19+: 44±3 vs 7.3±2***, n=6), and
increased the intracellular IFN-#- expressing T cells (% IFN-#+/
CD4+ cells before versus after the culture:
4.3±1.7 vs 12.0±4.6*; %
IFN-#+/CD8+:
8.9±5.4 vs 20.8±6.8*, n=5). Additionally, cultured
cells showed enhanced anti-MCC cytotoxicity
evaluated by JAM
test. By staining cells with CFSE prior to
their adoptive transference,
we were able to detect them within the
tumor tissue,
spleen and distant lymph node on day 7
after the innoculum.
Our results suggest that the anti-tumor
e'ects obtained with
the treatment are due, at least in part, to
anti-CD3+IL-2- induced
decrease of B cells and increase of IFN#+ T cells with enhanced
cytotoxic
capacity. (*p<0.05, **p<0.01, ***p<0.001).