A fresh look at tumor immunosurveillance and immunotherapy

Despite major advances in our understanding of adaptive immunity and dendritic cells, consistent and durable responses to cancer vaccines remain elusive and active immunotherapy is still not an established treatment modality. The key to developing an effective anti-tumor response is understanding why, initially, the immune system is unable to detect transformed cells and is subsequently tolerant of tumor growth and metastasis. Ineffective antigen presentation limits the adaptive immune response; however, we are now learning that the host's innate immune system may first fail to recognize the tumor as posing a danger. Recent descriptions of stress-induced ligands on tumor cells recognized by innate effector cells, new subsets of T cells that regulate tumor tolerance and the development of spontaneous tumors in mice that lack immune effector molecules, beckon a reflection on our current perspectives on the interaction of transformed cells with the immune system and offer new hope of stimulating therapeutic immunity to cancer.