About the Cover
The cover image is an artistic rendition of the complex biologic features of the CD4⁺ T-cell lineage and their contribution to tumor immunity. In response to developmental and environmental cues, CD4⁺ T cells differentiate into multiple subsets to orchestrate a broad range of effector activities during the initiation, expansion, and memory phase of a host immune response against pathogenic invasion, in regulating autoimmunity, and in shaping antitumor immunity.
Six major CD4⁺ T-cell subsets have been characterized with antitumor and/or protumor activity: CD4-CTL and T_H1 cells express immune molecules that promote tumor killing. T_FH, T_H2, and T_H17 cells have both antitumor and protumor activities. FoxP3⁺CD4⁺ regulatory T cells (Treg) are critically important for the maintenance of immune homeostasis and self-tolerance. However, tumor-induced factors promote the recruitment and expansion of Treg; intratumoral Treg suppress T-effector cell functions, impeding effective immunity against cancer, and high levels of CD4⁺ Treg in tumors correlate with poor prognosis. For details, see Masters of Immunology primer by Kim and Cantor on page 91 of this issue.

About the Master
Harvey Cantor, MD, is the Baruj Benacerraf Professor of Microbiology and Immunobiology at Harvard Medical School and chair of the Department of Cancer Immunology and AIDS at the Dana-Farber Cancer Institute. Dr. Cantor's educational and practical training includes a BA from Columbia University and an MD from the New York University School of Medicine, 2 years of fellowship training at the NIH campus in Bethesda, Maryland, 2 years as an NIH Special Fellow at the National Institute for Medical Research in Mill Hill, London, and a residency in medicine at the Stanford University Hospital.
In the early 1970s, T cells were thought to be a homogenous population of lymphocytes that were not B cells. Dr. Cantor's studies indicated that the thymus gave rise to two major lineages of T cells (T-helper [T_H] and T-cytotoxic [T_C]), which recognized the MHC class II and class I molecules, respectively, and which were equipped to mediate distinct immunologic functions before overt encounter with antigen. These experiments were based on the idea that the pattern of proteins expressed on the cell surface could be used to separate and define the developmental and functional components of the immune system. The Cantor laboratory used this approach to dissect cell-mediated immunity into its cellular components, to isolate natural killer (NK) cells, and to correlate T-cell surface phenotype with function and MHC restriction at the clonal level.
Recent studies from the Cantor lab have begun to define a lineage of CD8⁺ regulatory T cells (Treg) that are genetically programmed to inhibit the development of autoimmune disease and to regulate antitumor immunity via suppression of the activation and expansion of follicular helper T cells (T_FH). The Cantor lab has defined an interaction between dendritic cells and T cells that regulates the differentiation of T_H cell subsets after infection and have defined an inhibitory interaction between NK cells and autoreactive T cells that may regulate autoimmune disease.
Dr. Cantor is a member of the U.S. National Academy of Sciences and the American Academy of Arts and Sciences and a fellow of the American Association for the Advancement of Science. Many of the individuals he has mentored are now prominent immunologists, and several are members of the U.S. National Academy of Sciences and/or Institutes of Medicine, including Laurie Glimcher, professor of medicine and dean and provost of the Weill Cornell Medical College, Anjana Rao, professor at the La Jolla Institute for Allergy and Immunology, and Gary Nabel, past director of the NIH Vaccine Research Center and current Senior Vice President and Chief Scientific Officer of Sanofi.