Tak W. Mak is internationally known for his work on the genetics and molecular biology of cancer and the immune system. He has been a major figure in the fields of immunology and molecular and cellular biology for almost 40 years, and is a world leader in basic and translational research into the genetics of immunity and cancer. In 1984, he led the group that cloned the gene encoding a chain of the human T cell receptor. This discovery laid the ground work for our understanding of much of T cell biology and heralded the CAR-T technologies now approved for the treatment of leukemias and lymphomas. Dr. Mak’s lab was also a pioneer in the genetic modification of mouse strains (“knockout mice”) to identify factors associated with susceptibility to immune disorders or various cancers. The Mak team used these mutant animals to elucidate the functions of numerous molecules involved in immune responses, programmed cell death, and tumorigenesis, including the important tumour suppressors p53 and PTEN, and the breast cancer-related genes BRCA1 and BRCA2. Notably, in 1995, his group used mutant mice to show that CTLA4 is a negative regulator of T cell activation, paving the way for the development of T cell checkpoint inhibitor regulators as immunotherapeutic agents. Dr. Mak’s laboratory continues to develop novel approaches for designing and producing TCRs that are specific for antigens appearing on the surfaces of cancer cells. In a different vein of investigation, his team recently showed that the brain communicates with the immune system via T and B cells producing acetylcholine, a finding with implications for future treatments of cancer and autoimmune or neurodegenerative diseases. The Mak group continues to uncover immune cell subsets that can synthesize this prototypical neurotransmitter, and is delving into the novel functions of this molecule outside neurotransmission.