IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Lymphadenectomy exacerbates tumor growth while lymphadenectomy plus the adoptive transfer of autologous cytotoxic cells and low-dose cyclophosphamide induces regression of an established murine fibrosarcoma
Autor/es:
ANDREA MAGLIOCO; DAMIAN MACHUCA; JULIANA MUNDIÑANO; GABRIEL CABRERA; GABRIELA CAMICIA; JUAN BRUZZO; GABRIELA CAMERANO; HÉCTOR COSTA; RAÚL A RUGGIERO; GRACIELA I DRAN
Revista:
CANCER IMMUNOLOGY IMMUNOTHERAPY
Editorial:
SPRINGER
Referencias:
Año: 2010
ISSN:
0340-7004
Resumen:
Tumor-draining lymph node (TDLN) ablation is
routinely performed in the management of cancer; nevertheless,
its usefulness is at present a matter of debate. TDLN
are central sites where T cell priming to tumor antigens and
onset of the antitumor immune response occur. However,
tumor-induced immunosuppression has been demonstrated
at TDLN, leading to downregulation of antitumor reaction
and tolerance induction. Tolerance in turn is a main
impairment for immunotherapy trials. We used a murine
immunogenic fibrosarcoma that evolves to a tolerogenic
state, to study the cellular and molecular mechanisms
underlying tolerance induction at the level of TDLN and to
design an appropriate immunotherapy. We determined that
following a transient activation, the established tumor
induces signs of immunosuppression at TDLN that coexist
with local and systemic evidences of antitumor response.
Therefore, we evaluated the feasibility of removing TDLN
in order to eliminate a focus of immunosuppression and
favor tumor rejection; but instead, a marked exacerbation of
tumor growth was induced. Combining TDLN ablation with
the in vivo depletion of regulatory cells by low-dose
cyclophosphamide and the restoring of the TDLN-derived
cells into the donor mouse by adoptive transference, resulted
in lowered tumor growth, enhanced survival and a considerable
degree of tumor regression. Our results demonstrate
that important antitumor elements can be eliminated by
lymphadenectomy and proved that the concurrent administration
of low-dose chemotherapy along with the reinoculation
of autologous cytotoxic cells provides protection. We
suggest that this protocol may be useful, especially in the
cases where lymphadenectomy is mandatory.