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The methods and equipment used to probe cellular questions are rapidly advancing—including, at Yale, through the addition in 2014 of CyTOF, or Cytometry Time-Of-Flight, and this past June of the CyTOF Imaging Mass Cytometer (IMC), which greatly expands Yale's ability to examine specimens that are analyzed both for clinical diagnosis and for basic research.

Yale Cancer Center (YCC) researchers attended the 40th annual San Antonio Breast Cancer Symposium (SABCS), from December 5-9, and bringing news of major advances against a disease that strikes more than 250,000 women and men in the United States each year. The Symposium is a five-day program attended by an international audience of academic and private researchers and physicians from over 90 countries.

In a new study, a Yale-led research team identified the mechanism of a gene that raises the risk of severe rheumatoid arthritis in susceptible individuals. The finding may lead to the development of treatment based on the genetic profiles of arthritis patients, the researchers said.

David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses various options for biomarker testing in lung cancer. Genomics testing involves an examination of the mutational or neoantigen load, explains Rimm. While this assay does select patients with a high mutational load, Rimm feels that this method is insufficiently sensitive, such that it misses those patients who may not have a high mutational load, but would still benefit from therapy. Rimm is more optimistic about another form of biomarker testing, which involves looking at the immune cell microenvironment. In this method, one can measure the distribution and properties of T-cells determined by coexpression of other markers.

In a recent study, a Yale Cancer Center team compared the performance of the four available PD-L1 assay tests. They found that one of the assays failed to reveal comparable levels of PD-L1, a tumor-promoting protein, while three others revealed comparable levels. The findings were presented September 26 at the International Association for the Study of Lung Cancer (IASLC) 2016 Chicago Multidisciplinary Symposium in Thoracic Oncology in Chicago.

David L. Rimm, MD, PhD, professor of pathology and of medicine, director of pathology tissue services, director of translational pathology, Yale Cancer Center, discusses alternatives to PD-L1 testing to predict response with checkpoint inhibitors in lung cancer. Around 10% of patients who are PD-L1 negative still show some benefit from a PD-1 inhibitor. A test is needed to identify those patients, says Rimm. There are a number of other potential approaches that are being considered, including genomic approaches, neoantigen-type approaches, and other protein or alternative microenvironment-type approaches. Genomic and neoantigen approaches are less likely to succeed, say Rimm.

When doctors do take biopsies, they want to do so in a way that is safest for patients, says Roy Herbst, a lung cancer oncologist at the Yale School of Medicine in New Haven. In lung cancer, for example, the oncologist might choose not to take biopsies of metastases from the liver, because these extra biopsies could lead to bleeding complications. “Remember, you are sticking a needle through the skin using guided imaging for most of these,” Herbst says.

A novel Yale study answers age-old questions about how cancers spread by applying tools from evolutionary biology. The new insights will help scientists better understand the genetic origins of tumor metastases, and lead to more effective targets for treatment, said the researchers. The study, led by associate professor of public health (biostatistics) Jeffrey Townsend, was published on Feb. 8 by the Proceedings of the National Academy of Sciences.