[Significance of immune checkpoints in lymphoid malignancies]

Immune checkpoint blockade has been widely applied for the treatment of malignant tumors, including hematological malignancies. Nevertheless, growing evidence has indicated that there are specific situations in which somatic or germline abnormalities in gene coding for immune checkpoint-associated molecules may play a role in the development and progression of lymphoid malignancies. Somatic mutations in the PDCD1 gene and generation of the CTLA4-CD28 fusion gene have been reported in T-cell lymphomas and are considered to be involved in disease progression. By contrast, rare germline variants in CTLA4 and HAVCR2 are suggested to be associated with the predisposition to immunodeficiency-associated lymphomas and subcutaneous panniculitis-like T-cell lymphoma, respectively. Abnormalities in the associated molecules may alter the properties of lymphocytes and contribute to cellular transformation because immune checkpoints modulate the activities and functions of lymphocytes. Many new therapies targeting immune checkpoints are under development and have been applied in clinics, and notably, immune checkpoint blockade may lead to an unexpected deterioration in health or the development of new lymphoid malignancies in some specific situations.