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L-arginine depletion by regulatory cells and cancer cells expressing arginase-1 (Arg-1) is a vital contributor to the immunosuppressive tumor microenvironment in patients with cancer. We have recently described the existence of pro-inflammatory effector T cells that recognize Arg-1. Hence, Arg-1-specific self-reactive T cells are a naturally occurring part of the memory T-cell repertoire of the human immune system. Here, we further characterize a highly immunogenic epitope from Arg-1. We describe frequent T-cell-based immune responses against this epitope in patients with cancer, as well as in healthy donors. Furthermore, we show that Arg-1-specific T cells expand in response to the TH2 cytokine interleukin (IL)-4 without any specific stimulation. Arg-1-specific memory TH1 cells that respond to increased IL-4 concentration may, therefore, drive the immune response back into the TH1 pathway. Arg-1-specific T cells thus appear to have an important function in immune regulation. Because Arg-1 plays an important role in the immunosuppressive microenvironment in most cancers, an immune modulatory vaccination approach can readily be employed to tilt the balance away from immune suppression in these settings.

The JAK2 V617F mutation is a target for specific T cells in the JAK2 V617F-positive myeloproliferative neoplasms

Recently, there has been an increased focus on the immune checkpoint protein PD-1 and its ligand PD-L1 due to the discovery that blocking the PD-1/PD-L1 pathway with monoclonal antibodies elicits striking clinical results in many different malignancies. We have described naturally occurring PD-L1-specific T cells that recognize both PD-L1-expressing immune cells and malignant cells. Thus, PD-L1-specific T cells have the ability to modulate adaptive immune reactions by reacting to regulatory cells. Thus, utilization of PD-L1-derived T cell epitopes may represent an attractive vaccination strategy for targeting the tumor microenvironment and for boosting the clinical effects of additional anticancer immunotherapy. This review summarizes present information about PD-L1 as a T cell antigen, depicts the initial findings about the function of PD-L1-specific T cells in the adjustment of immune responses, and discusses future opportunities.