TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Abstract: Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.
TL;DR: A unifying conceptual framework called “cancer immunoediting,” which integrates the immune system’s dual host-protective and tumor-promoting roles is discussed.
Abstract: Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. Here, we discuss a unifying conceptual framework called "cancer immunoediting," which integrates the immune system's dual host-protective and tumor-promoting roles.
TL;DR: The historical and experimental basis of cancer immunoediting is summarized and its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction are discussed.
Abstract: The concept that the immune system can recognize and destroy nascent transformed cells was originally embodied in the cancer immunosurveillance hypothesis of Burnet and Thomas. This hypothesis was abandoned shortly afterwards because of the absence of strong experimental evidence supporting the concept. New data, however, clearly show the existence of cancer immunosurveillance and also indicate that it may function as a component of a more general process of cancer immunoediting. This process is responsible for both eliminating tumors and sculpting the immunogenic phenotypes of tumors that eventually form in immunocompetent hosts. In this review, we will summarize the historical and experimental basis of cancer immunoediting and discuss its dual roles in promoting host protection against cancer and facilitating tumor escape from immune destruction.
TL;DR: The genetic findings provide evidence for immunoediting in tumors and uncover mechanisms of tumor-intrinsic resistance to cytolytic activity, suggesting immune-mediated elimination.
TL;DR: The history of the cancer immunosurveillance controversy is summarized and its resolution and evolution into the three Es of cancer immunoediting--elimination, equilibrium, and escape are discussed.
Abstract: After a century of controversy, the notion that the immune system regulates cancer development is experiencing a new resurgence. An overwhelming amount of data from animal models--together with compelling data from human patients--indicate that a functional cancer immunosurveillance process indeed exists that acts as an extrinsic tumor suppressor. However, it has also become clear that the immune system can facilitate tumor progression, at least in part, by sculpting the immunogenic phenotype of tumors as they develop. The recognition that immunity plays a dual role in the complex interactions between tumors and the host prompted a refinement of the cancer immunosurveillance hypothesis into one termed "cancer immunoediting." In this review, we summarize the history of the cancer immunosurveillance controversy and discuss its resolution and evolution into the three Es of cancer immunoediting--elimination, equilibrium, and escape.