Titles and Affiliations
Deputy Director, Sandra and Edward Meyer Cancer Center
Margaret and Herman Sokol Professor of Oncology Research
Professor of Pharmacology
Research area
Improving response to immunotherapy in breast cancer patients.
Impact
Immunotherapy is a treatment strategy that utilizes the body’s immune defenses to fight disease. Immune checkpoint blockade (ICB) is an innovative cancer treatment that uses a class of drugs known as immune checkpoint inhibitors that are designed to help the immune system recognize and destroy cancerous cells. This treatment strategy has been effective in patients with melanoma, lung, and other cancers, but has not been very effective for most breast cancers. The BCRF-supported research of Drs. Merghoub and Wolchok focuses on both developing new immune-based strategies and improving response to existing immunotherapies in breast cancer.
Progress Thus Far
Previously Drs. Merghoub and Wolchok pioneered approaches targeting tumor metabolism to restore anti-tumor immunity. The team found that lactate, a metabolic byproduct produced by tumor-associated neutrophils is an important driver of immune suppression. Inhibiting the export of lactate restored sensitivity to ICB in tumors that had previously been resistant. The team confirmed and extended these findings in a different type of immunotherapy called adoptive T cell therapy (ACT) where the patient’s immune cells are removed from the body, either expanded or reengineered in the laboratory, and reinfused in the body to attack tumors. Limiting lactate production in this model also restored anti-tumor immunity.
What’s next
Drs. Merghoub and Wolchok will continue to develop new metabolic-based strategies to enhance ICB in breast cancer. In the upcoming year, they will evaluate inhibition of tumor glycolysis to enhance ACT and will test targeting of the lactate transporter MCT4 specifically in neutrophils to restore immunotherapy responses. To complement this work, they will correlate MCT4 expression in TNBC patient samples with clinical outcomes.
Biography
Taha Merghoub, PhD is the deputy director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. He received his BA degree from University of Algiers, Algeria, and MS and PhD degrees with highest distinction from University of Paris, France. His thesis work focused on the study of genetic polymorphism in fetal hemoglobin genes in patients with sickle cell anemia and thalassemia. His findings provided insight to the correlation of genotypes and phenotypes in sickle cell anemia and thalassemia. After graduation, he pursued his postdoctoral research with Dr. Pier Paolo Pandolfi at Memorial Sloan Kettering Cancer Center. He characterized the transcriptional properties of the Pokemon gene and its role during development. He also played an active role in the generation of laboratory models for acute promyelocytic leukemia and furthered his knowledge and experience in genetics.
