ABOUT THE COVER
The observation of lymphocytes and mononuclear cells associated with human cancer was first noted more than a century ago, and their importance in host defense against tumors and their potential role in disease prognosis have been studied and characterized extensively in the past half century. The cover image shows lymphocyte infiltration into melanomas. On the upper left is a light microscopy image of a typical tertiary lymphoid structure (large central oval of packed blue-stained lymphocytes) stained by H&E that is associated with melanoma metastases in the lungs of a patient with stage IV disease. These so-called “immune microterritories” are thought to be involved in local B-cell and T-cell reactivity within the melanoma microenvironment. On the lower right is a light microscopy image of the vertical growth phase of a primary malignant melanoma. The tumor (two central melanoma cells shown) is diffusely infiltrated with lymphocytes (dark nuclei) and qualifies as a dense, brisk infiltrate associated with a favorable prognosis. (Image on upper left generated by Jane Messina, a senior member of the Departments of Anatomic Pathology and Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL; image on lower right generated by Labib R. Zakka, Research Fellow, Dermatology Department, Brigham and Women's Hospital, and Adriano Piris, Instructor in Pathology, Harvard Medical School, and codirector of the Mihm Cutaneous Pathology Consulatative Service, Boston, MA.).

ABOUT THE MASTERS
This month's Masters Primer on the histopathology of tumor-infiltrating lymphocytes (TIL) in melanoma and the host immune response is coauthored by two luminaries in immunopathology, Martin C. Mihm Jr and James J. Mulé.
Dr. Mihm is a professor of pathology and dermatology at Harvard Medical School (HMS) and the associate director of the melanoma program at the Dana-Farber Brigham and Women's Cancer Center. Dr. Mulé is the associate center director for translational science, the Michael McGillicuddy Endowed Chair for Melanoma Research and Treatment, and the scientific director of Cell-based Therapies at the Moffitt Cancer Center in Tampa, Florida.
Dr. Mihm was named the 2003 Legend in Dermatopathology of the American Society of Dermatopathology. His research interests have principally been related to malignant melanoma. He began his studies on melanomas with Wallace Clark in 1965 and coauthored the first publication of the classification of malignant melanoma into subtypes. For two decades, Dr. Mihm codirected the WHO melanoma pathology program, which was devoted mainly to the study of TILs in melanoma and has made significant contributions to establishing the importance of TILs as a prognostic factor in primary and metastatic melanoma. In the late 1970s, Dr. Mihm studied delayed hypersensitivity reactions in animals and humans with Harold F. Dvorak, author of the January 2015 Masters primer entitled “Tumors: Wounds That Do Not Heal—Redux.” Dr. Mihm's collaboration with Dr. Dvorak led to the discovery of the role of basophils in human hypersensitivity reactions, and a definitive description of delayed hypersensitivity in humans that, in turn, led to the first description of the role of the vasculature in human allograft rejection. In the past decade, along with physician-scientist Paula North, Dr. Mihm has begun to study the pathogenesis of vascular anomalies in children and adults. The two researchers discovered a specific phenotype in infantile hemangiomas, and they are investigating the pathogenesis of these lesions. In 1994, Dr. Mihm began collaborations with Glenn Dranoff and F. Stephen Hodi to study vaccine reactions to autologous melanoma cells and the various factors affecting host immune response and survival. This work has led to critical insights in the dynamics of immune function and its regulation. Dr. Mulé began his studies in tumor immunology and immunopathology under the mentorship of Karl Erik and Ingegerd Hellstrom at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, Washington, soon after it opened its doors in 1975. There, he showed for the first time that lymphocytes could selectively localize in tumors in vivo. In 1981, Dr. Mulé moved to the Surgery Branch of NCI to study under Steven A. Rosenberg, publishing a series of studies on the antitumor effect of lymphokine-activated killer cells plus recombinant IL2, the mechanisms operative in high-dose IL2 therapy, and the enhancement of therapeutic potency of cytokine gene-modified tumor cells and TILs. Dr. Mulé's research group is now involved in characterizing and validating genomic signatures of immunotherapy response, as well as designing and testing novel dendritic cell–based vaccine and adoptive T-cell transfer strategies in preclinical animal tumor models. The aim of their work is to improve these approaches through a focus on breaking tolerance to tumor self-antigens by inhibiting regulatory cells, boosting T-cell costimulation, and administering combinations of recombinant cytokines and other defined molecules with immune-enhancing activities.
Drs. Mihm and Mulé have received numerous awards and recognitions. Dr. Mihm is particularly proud of his teaching and mentoring awards and Dr. Mulé of his trainees who now hold research and teaching positions world-wide. Drs. Mihm and Mulé serve on the editorial boards of leading peer-reviewed journals and on the scientific advisory boards of various academic and health institutions as well as biotechnology and pharmaceutical companies.
Dr. Mihm was born in Pittsburgh, Pennsylvania and graduated summa cum laude from Duquesne University. He obtained his MD from the University of Pittsburgh Medical Center. He completed his residency in dermatology and pathology at the Massachusetts General Hospital (MGH) and subsequently joined the MGH staff. In 1976, he founded one of the first five U.S. residency training programs in dermatopathology. In 1993, he joined the faculty of Albany Medical Center to establish a dermatology and dermatopathology training program. He returned to MGH in 1996 as a clinical professor to continue work in melanoma and to establish a vascular malformation clinic. Dr. Mihm holds five adjunct professorships at different schools in the United States. He cofounded the Rare Tumor Institute of the WHO in Milan, Italy, and was its external coordinator for 5 years. He is currently the codirector of the melanoma pathology program of the European Organisation for the Research and Treatment of Cancer. He has written over 500 articles and authored or coauthored 12 books.
Dr. Mulé was born in Kearny, New Jersey, and graduated from the New Jersey City University; he received a special individual PhD from the FHCRC and the University of Washington, Seattle. He is a long-standing special government employee with the FDA (CBER) and NCI. He chaired the Cellular, Tissue, and Gene Therapy Advisory Committee of CBER, FDA, and was a member of the NCI Director's Board of Scientific Counselors (BSC-A). He has written over 200 articles and has been a continuously funded investigator for nearly 25 years. Dr. Mulé received postgraduate training at the Surgery Branch of NCI, where he became a senior investigator with tenure. After helping to launch and scientifically direct two biotechnology companies in Palo Alto, California, Dr. Mulé was named the inaugural director of the Graduate Program in Immunology and director of the Tumor Immunology and Immunotherapy Program at the University of Michigan, where he was also the Maude T. Lane Endowed Professor of Surgery and a professor in the Department of Internal Medicine.