Thierry Dorval | Search PubMed

PubMed2003

[Anemia and immunotherapy].

Immunotherapy of cancer is an old concept and specific or non specific approaches have been developed for decades. These early trials have never demonstrated any benefit and have largely been abandoned. The advent of recombinant techniques allowing to produce large amounts of cytokines, the recent description of tumour antigens expressed by tumor cell surface, the rapid increase in immunological knowledge and the development of molecular biology have rekindled interest in immunological therapy of cancer. Extensive clinical experience using cytokines and more recently monoclonal antibodies is now available and allows us to report on immunotherapy-induced anemia.

Anemia↗

PubMed2002

Modulation of tumor growth by inhibitory Fc(gamma) receptor expressed by human melanoma cells.

The efficacy of anti-tumor IgG reflects the balance between opposing signals mediated by activating and inhibitory Fc(gamma) receptors (Fc(gamma)Rs) expressed by effector cells. Here, we show that human malignant melanoma cells express the inhibitory low-affinity Fc(gamma) receptor Fc(gamma)RIIB1 in 40% of tested metastases. When melanoma cells were grafted in nude mice, a profound inhibition of Fc(gamma)RIIB1 tumor growth that required the intracytoplasmic region of the receptor was observed. IgG immune complexes (ICs) may be required for this inhibition, since sera from nude mice bearing tumors contained IgG that decreased the proliferation of Fc(gamma)RIIB1-positive cells in vitro, and tumor development of Fc(gamma)RIIB1-positive melanoma lines was not inhibited in antibody-defective severe combined immunodeficiency (SCID) mice. Passive immunization of SCID mice with anti-ganglioside G(D2) antibody resulted in significant inhibition of growth of Fc(gamma)RIIB1-positive tumors in an intracytoplasmic-dependent manner. Altogether, these data suggest that human melanoma cells express biologically active inhibitory Fc(gamma)RIIB1, which regulates their development upon direct interaction with anti-tumor antibodies. Therefore, Fc(gamma)R expression on human tumors may be one component of the efficacy of antibody-mediated therapies, and Fc(gamma)R-positive tumors could be the most sensitive candidates for such treatments.

Animals↗