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Human Tumor Gangliosides Inhibit Murine Immune Responses in Vivo¹

Center for Cancer and Transplantation Biology, Children's Research Institute, and Departments of Pediatrics and Biochemistry/Molecular Biology, George Washington University School of Medicine, Washington, DC 20010

Gangliosides which are shed by tumor cells clearly inhibit cellular immune responses in vitro. However, the immunosuppressive activity of these molecules have been more difficult to ascertain in vivo. Here we have adapted a murine model to determine the effects of tumor gangliosides in an in vivo microenvironment, the lymph node draining the site of stimulation by allogeneic cells. In this model, allogeneic splenocytes (BALB/c) are s.c. injected into C3H mice. The cellular immune response in the draining popliteal lymph nodes 4 days later is evidenced as an increase in lymph node mass (2-fold), lymphocyte number (6-fold), and lymphocyte DNA synthesis (6-fold). Purified human neuroblastoma gangliosides (10 nmol) coinjected with the stimulating allogeneic cells significantly suppressed this in vivo immune response. The increase in the lymph node mass was reduced by 65% (0.66 versus 1.89 mg), the increase in lymphocyte number (4.0 x 10⁶ cells/node) was almost completely inhibited (1.1 x 10⁶ cells/node), and in vitro [³H]thymidine uptake by the lymphocytes recovered in vivo was reduced by 80%. In contrast to the inhibition by tumor gangliosides, liposomes of cholesterol:lecithin were not inhibitory. Thus, tumor gangliosides, specifically, modulate cellular immune responses in vivo, which may contribute to the observed enhancement of tumor formation by these molecules.

¹ This work was supported by Grants CA42361 and CA66010 from the National Cancer Institute and by a grant from the Phi Beta Psi Sorority.

² To whom correspondence and requests for reprints should be addressed, at Center for Cancer and Transplantation Biology, Children's Research Institute, 111 Michigan Avenue, NW, Washington, DC 20010.

Received 11/14/94. Accepted 12/ 1/94.

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