On The Trait Undetectable Immunogenicity of Murine Spontaneous Tumors

DANIELA MONTAGNA; GRACIELA DRAN; PAULA CHIARELLA; ARIEL STRAZZA; RAÚL RUGGIERO

Mar del Plata

Congreso; LXI Reunión Científica Anual de la SociedadArgentina de Investigación Clínica (SAIC) y LXIV de la Sociedad Argentina de Inmunología; 2016

SAI-SAIC

Most murine and rat tumors of spontaneous origin display no evidence of immunogenicity, a feature putatively shared with many human tumors. Herein, using three murine tumors exhibiting undetectable immunogenicity called CEI, C7HI and LMM3, we have investigated whether that feature can be attributed to absence of tumor antigens or to the existence of tolerogenic mechanisms that prevent such antigens from initiating an antitumor immune response. To discriminate between both alternatives and extending preliminary observations, we used the strategy to mix in vitro lethally irradiated (LI) tumor cells from the non-immunogenic tumors with LI cells from a strongly immunogenic chemically-induced tumor (called MC-C). The mixture was then inoculated s.c. in mice 14 and 7 days before the challenge with different doses of live cells from the non-immunogenic tumors. DT 50 (mean ± SE) of CEI tumor: Control Group: 13,000 ± 2,000; Group pretreated with LI CEI cells: 8,200 ± 2,000; Group pretreated with LI MC-C cells: 9,800 ± 1,500; Group pretreated with the mixture of LI CEI cells + LI MC-C cells: 52,000 ± 5,000 (p < 0.02 vs. Control, mean of two experiments). Similar results were obtained with C7HI and LMM3 tumors, that is, the pretreatment with the mixture produced a slight but consistent immunizing effect against the growth of the three non-immunogenic tumors and this effect was not associated with cross antigenicity between MC-C and the other tumors. Additional data revealed that the non-immunogenic tumors produced low levels of HGMB and Hsp60 danger signals for dendritic cell (DC) maturation and bore PDL-1 in the cellular surface. In contrast, MC-C tumor produced high levels of those danger signals and did not exhibit PDL-1.As a whole, these results suggested that our non-immunogenic murine tumors bear specific tumor antigens which on their own cannot initiate an anti-tumor immune response but in the context of maturational signals of DC provided by LI MC-C tumor cells can do.