Cancer Immunology

Program Overview

The immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of failures in immunity. Cancer cells that express mutant proteins manage to escape detection and elimination by the immune system. Chronic infections that persist due to incompletely effective immune responses also contribute to cancer. Some, such as human papillomavirus (HPV) and Epstein-Barr virus (EBV) are directly oncogenic, while others such as H. pylori, hepatitis C virus, hepatitis B virus and Chlamydia psittaci promote cancers by inducing chronic but ineffective immune stimulation. Similarly, chronic autoimmunity is linked to lymphoid malignancies or, in the case of inflammatory bowel disease, to colon carcinoma. Machinery that evolved for the generation of antigen receptor diversity on immune cells is co-opted in oncogenesis. On the other hand, the potency and specificity of the immune system can be a powerful tool that eliminates neoplastic cells. The success of the antibody Rituxan in treating CD20+ lymphomas and allogeneic stem cell transplantation (alloSCT) in treating hematopoietic malignancies highlights the potential of both antibody and T cell-based therapies. Nevertheless, immunotherapy of cancer is clearly in its infancy and recent and ongoing advances in basic immunology only now make it possible to more rationally explore the potential of the adaptive immune system to treat cancer.
With this background in mind, the goals of the Cancer Immunology Program are to:

  1. Elucidate the fundamental nature of molecular and cellular mechanisms of immunity. Basic research in immunology is conducted in four thematic areas: a) antigen presentation, b) T cell responses and their regulation, c) innate immunity and the links between the innate and adaptive immune system, and d) B cell function and cell biology. Seminal discoveries made at Yale in the fields of antigen processing, antigen cross-presentation, Toll-like receptor (TLR) function and mechanisms of T cell regulation and polarization have already begun to influence studies in the clinic. 
  2. Encourage research in human cancer immunology. The Cancer Immunology Program has a core group of investigators that use mice to investigate cancer immunity in models of allogeneic stem cell transplantation, melanoma, breast cancer, HPV infection and cutaneous malignancy. This work is strongly supported by the outstanding immunology research in non-cancer specific models. Since communication between these two groups is essential to achieve this end, a major goal is to ensure that such interactions remain effective and robust.
  3. Develop and implement novel investigator-initiated trials in cancer immunotherapy. The Cancer Immunology Program has ongoing programs and therapeutic trials in allogeneic stem cell transplantation, extracorporeal photopheresis, melanoma immunotherapy, and vaccine development.

Highlighted Research Articles

How Immune Cells Go Rogue - Researchers identified an enzyme called arginase 1 (ARG1) that plays a critical role in promoting tumor development. Further, they discovered that removing this enzyme decreased the size of tumors by half.
A One-Two Punch Against Melanoma - In a Phase I trial at Yale Cancer Center, a new combination of drugs proved highly effective against melanoma. Patients in the trial were treated with two antibodies, ipilimumab and nivolumab.

New Links Between Inflammation and Colon Cancer - "Chronic tissue damage predisposes patients to the development of cancer, particularly in the intestine.” - Dr. Richard A. Flavell. Dr. Flavell is investigating how auto-inflammatory diseases are triggered.

Testing a New Approach to Make Stem Cell Transplantation Safer for Patients - “We’re hopeful that depletion of naïve T cells will result in less GVHD and better immune reconstitution.” – Dr. Warren Shlomchik.