The tumor antigen NGcGM3 is a human CD1d ligand capable of mediating B and NKT cells interaction

MARIA VIRGINIA GENTILINI; M EUGENIA PEREZ; PABLO FERNANDEZ; LEONARDO FAINMBOIM; ELOISA ARANA

CANCER IMMUNOLOGY IMMUNOTHERAPY

SPRINGER

Lugar: Berlin; Año: 2016 vol. 65 p. 551 - 562

0340-7004

The expression of ganglioside N-glicolil GM3 (NGcGM3) in human is restricted to cancer cells, by definition a tumour antigen (Ag). There are measurable quantities of circulating aNGcGM3 antibodies (Ab) in human serum. Interestingly, some people have circulating Ag specific IgGs, capable of complement-mediated cytotoxicity against NGcGM3 positive cells, relevant for tumour surveillance. In light of the Ag?s chemical nature, we postulated it as a candidate ligand for CD1d. Furthermore, we hypothesize that the immune mechanism involved in the generation of such antibodies entailed a cross talk between B lymphocytes (Bc) and iNKT cells. Combining cellular techniques as flow cytometry and a non-cellular biochemical assay, we demonstrated that CD1d binds NGcGM3 and that human Bc present NGcGM3 in a CD1d context, by two alternative strategies. We also showed that a fraction of that binding needs living cells. Finally, by co culturing primary human Bc with iNKT cells and measuring Ki 67 expression, we detected a reproducible increment in proliferation of both cell populations when Ag was on the medium. Our findings identify a novel, endogenous, human CD1d ligand. Moreover, they suggest that expression of NGcGM3 on tumor cells may prime an effective iNKT dependent antitumor antibody response, through cooperation with B cells, an immunological mechanism that has not been described before for humans.