Increasing microenvironment complexity in HL

Abstract

cHL is unique among lymphoid malignancies, given that malignant HRSC comprise less than 1% of the total cell population. HRSC secrete chemokines and cytokines that drive the formation of a complex microenvironment of nontumor cells. This microenvironment consists of both innate as well as adaptive immune cells.2 The extensive but ineffective immune cell infiltrates found in cHL suggest that HRSC have developed mechanisms to escape immunosurveillance. Furthermore, HRSC depend on microenvironmental signals for survival and growth. Even though many cHL patients are cured with current treatment regimens, 20% to 30% fail to respond or experience a relapse after treatment. Moreover, especially in adolescents and young adults, treatment-related toxicity and long-term morbidity are persistent challenges requiring more basic research to identify new therapeutic targets, particularly within this unique microenvironment.3,4 Stewart et al provide evidence for the first time of the expression of immunoregulatory checkpoints and the secretion of chemokines from previously uncharacterized cells that contribute to the exhaustion of T cells and contribute to immune evasion in cHL.