Immune and Inflammatory Cells of the Tumor Microenvironment Represent Novel Therapeutic Targets in Classical Hodgkin Lymphoma

Abstract

Classical Hodgkin Lymphoma (cHL) is a B-cell malignancy that, typically, responds well to standard therapies. However, patients who relapse after standard regimens or are refractory to induction therapy have a dismal outcome. The implementation of novel therapies such as the anti-CD30 monoclonal antibody Brentuximab Vedotin and immune checkpoint inhibitors has provided curative options for many of these patients. Nonetheless, responses are rarely durable, emphasizing the need for new agents. cHL is characterized by a unique microenvironment in which cellular and humoral components interact to promote tumor survival and dissemination. Knowledge of the complex composition of cHL microenvironment is constantly evolving; in particular, there is growing interest in certain cell subsets such as tumor-associated macrophages, myeloid-derived suppressor cells and neutrophils, all of which have a relevant role in the pathogenesis of the disease. The unique biology of the cHL microenvironment has provided opportunities to develop new drugs, many of which are currently being tested in preclinical and clinical settings. In this review, we will summarize novel insights in the crosstalk between tumor cells and non-malignant inflammatory cells. In addition, we will discuss the relevance of tumor-microenvironment interactions as potential therapeutic targets.

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

“…regulatory T cells (Tregs) and Tumor associated macrophages (TAMs)). 5 , 6 Their complex interactions within the HL microenvironment have been well summarized and discussed. 5 – 8 This review will focus on the contribution of trogocytosis, 9 , 10 also called transendocytosis, 11 to the establishment of the immunosuppressive microenvironment in HL.…”

Role of Heterotypic Neutrophil-in-Tumor Structure in the Prognosis of Patients With Buccal Mucosa Squamous Cell Carcinoma

“…Neutrophils are the most well-known marker and promoter of inflammation (9). Recent findings have indicated that inflammation, metabolic response, and immune response are the three main components of tumor microenvironment, which are of significance in cancer pathogenesis and progression by interacting with tumor cells (9)(10)(11)(12)(13). Several chemokines, cytokines and angiogenic factors produced by neutrophils may result in inflammatory cell recruitment and activation that crucially impact the tumor microenvironment, which could facilitate tumor cell proliferation, microvascular regeneration and tumor progression (9,14,15).…”

Methodological framework for radiomics applications in Hodgkin’s lymphoma

“…Conversely, R/R patients may be biologically more homogeneous, since treatments might result in resistant clones' selection. Moreover, the non-neoplastic cells of tumor microenvironment have been claimed as one of the main determinants responsible for pathogenesis and progression of HL (Mottok & Steidl, 2018;Calabretta et al, 2019). Infiltration of the tumor microenvironment by CD68+ and CD163+ macrophages, Treg and CD4 + T cells (especially with Th2 phenotype), and high CD4/CD8 ratio is associated to the emergence of resistance to conventional therapy, and a worse prognosis.…”