The goal of cancer immunotherapy is to restore and optimize the immune response against malignant clones through several stages, from recognition of tumor antigens to establishment of long-lived memory cell populations. Boosting the intrinsic anti-tumor immune responses of the patients’ own, several types of “active immunotherapies” have been tried in many types of malignancies, inspired by successful experiences of immune checkpoint inhibition even in Hodgkin lymphoma. However, in B-cell non-Hodgkin lymphomas, clinical usefulness of such “active immunotherapies” is relatively unsatisfactory considering the remarkable advances in “passive immunotherapy,” including CD19-targeting chimeric antigen receptor T-cell therapy. Understanding how tumor cells and immune cells interact and contribute to immune evasion processes in the tumor microenvironment (TME) is an important prerequisite for the successful restoration of anti-tumor immune responses. In this review, a recent understanding of the biology of the immune tumor microenvironment surrounding B-cell non-Hodgkin lymphomas will be introduced. In addition, novel therapeutic approaches targeting the immune microenvironment other than immune checkpoint blockade are discussed.

Keywords: Lymphoma, T cell, Regulatory T cell, Immunotherapy, Vaccine