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[Business Office Feature] Webinar Deciphering cancer: Modulating immunoregulatory pathways to treat tumors

Science

In addition to being the first line of defense against pathogenic attack, the immune system seeks out aberrant cells within the body that may become cancerous. In response, precancerous and cancerous cells may exploit immune checkpoint pathways to evade immune detection and destruction. In order to block these tumorigenic cells, novel therapeutics that modulate immune checkpoint signaling have been developed, with some already available and others in clinical trials. Further development of effective therapeutics for use in personalized medicine requires the identification and characterization of a diverse range of immune checkpoint biomarkers. This webinar will explore recent progress and future directions in translational and clinical efforts centered on checkpoint modulators and combination therapies matched to the molecular profile of individual tumors and the genetic background of patients.


Skin cancer therapy wins Nobel prize

BBC News

Two scientists who discovered how to fight cancer using the body's immune system have won the 2018 Nobel Prize for physiology or medicine. The work by James P Allison, from the US, and Tasuku Honjo, from Japan, has led to treatments for advanced, deadly skin cancer. Immune checkpoint therapy has revolutionised cancer treatment, said the prize-giving Swedish Academy. Experts say it has proved to be "strikingly effective". Allison, a professor at the University of Texas, and Honjo, a professor at Kyoto University, will share the Nobel prize sum of nine million Swedish kronor - about $1.01 million or 870,000 euros.


Enhancing responses to cancer immunotherapy

Science

Immune checkpoint blocking therapies (ICBs) that target T cell inhibitory receptors (immune checkpoints) have been implemented in the clinic to treat a variety of malignancies. To exemplify the potential success of these therapies, the 3-year overall survival for advanced melanoma has increased from 12% before 2010, when standard of care was chemotherapy, to 60% using ICBs (1). However, ICBs fail many patients (10 to 60% of treated patients respond, depending on cancer type), raising the obvious question of why. On page 582 of this issue, Chowell et al. (2) report that the success of ICBs is remarkably dependent on the ability to present diverse tumor antigens to T cells.


Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade

Science

The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached.


Genetic biomarker for cancer immunotherapy

Science

T cells eliminate pathogens by recognizing foreign proteins that are expressed on the cell surface (antigens). T cell activation in response to antigen occurs for a controlled period of time and is stopped by the expression of immune checkpoint proteins (1). Allison and colleagues proposed that antibody blockade of these proteins would enable prolonged T cell responses against cancer cells (2). The preclinical and clinical data that emerged using antibodies against two immune checkpoint proteins, cytotoxic T lymphocyte-associated protein 4 (CTLA4) and programmed cell death receptor-1 (PD-1), led to a paradigm shift in oncology as the treatment of some patients with these drugs led to tumor regression and durable survival for more than a decade (3). But as more patients with various types of cancer have been treated with immune checkpoint therapies, an enduring problem is to identify which patients are likely to respond.