IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity

Abstract

Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice do not completely lack functional T cells and that two components of the immune system-IFNgamma and perforin-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFNgamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.

Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery

“…These data are consistent with those reported for IFN-␥ production by homeostasis-induced memory CD8 T cells (8). IFN-␥ has not only been shown to correlate with antitumor effects of immunotherapies in vivo, but also to help prevent tumor formation in vivo (28). Although tumor lysate pulsing of the DC is required for optimal antitumor activity, in some instances we have observed that repetitive immunizations with unpulsed DC could induce a nonspecific response in the BMT setting but not in conventional, fully immunocompetent mice (data not shown).…”

Identification of target actin content and polymerization status as a mechanism of tumor resistance after cytolytic T lymphocyte pressure

“…The coexistence in cancer patients of tumor cells and tumorspecific circulating CD8ϩ T cells remains an intriguing paradox of tumor immunology (26,27). Our present results provide further evidence for the concept of immune selection in neoplastic development by showing that CTL selection pressure can lead to a striking adaptation of the tumor target, involving morphological change to escape immune surveillance.…”

Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis

“…4). Some MCA-induced sarcomas derived from RAGdeficient mice were previously reported to be unedited and rejected by a combination of CD8 ϩ and CD4 ϩ T cells in WT mice (27). MyD88 Ϫ/Ϫ mice were able to reject these highly immunogenic regressor MCA sarcomas (27) as efficiently as WT mice (Fig.…”