Abstract
Tumour-associated macrophages (TAMs) have been associated with survival in classic Hodgkin lymphoma (cHL) and other lymphoma types. The maturation and differentiation of tissue macrophages depends upon interactions between colony-stimulating factor 1 receptor (CSF1R) and its ligands. There remains, however, a lack of consistent information on CSF1R expression in TAMs. A new monoclonal antibody, FER216, was generated to investigate CSF1R protein distribution in formalin fixed tissue samples from 24 reactive lymphoid tissues and 187 different lymphoma types. We also analysed the distribution of CSF1R+, CD68+ and CD163+ macrophages by double immunostaining, and studied the relationship between CSF1R expression and survival in an independent series of 249 cHL patients. CSF1R+ TAMs were less frequent in B-cell lymphocytic leukaemia and lymphoblastic B-cell lymphoma than in diffuse large B-cell lymphoma, peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma and cHL. HRS cells in cHL and, with the exception of three cases of anaplastic large cell lymphoma, the neoplastic cells in NHLs, lacked detectable CSF1R protein. A CSF1R+ enriched microenvironment in cHL was associated with shorter survival in an independent series of 249 cHL patients. CSF1R pathway activation was evident in the cHL and inactivation of this pathway could be a potential therapeutic target in cHL cases.
Highlights
The presence of a characteristic inflammatory microenvironment is a fundamental component of the tumour mass in classical Hodgkin lymphoma [1]
An episomal expression system based on Epstein-Barr virus (EBV) components was used for recombinant colony-stimulating factor 1 receptor (CSF1R) production in mammalian cells (HEK293)
Sequential IP and western blot (WB) studies demonstrating that FER216 recognised proteins immunoprecipitated by clone 61701 further confirmed the specificity of FER216 for CSF1R (Fig 1C)
Summary
The presence of a characteristic inflammatory microenvironment is a fundamental component of the tumour mass in classical Hodgkin lymphoma (cHL) [1]. The neoplastic Hodgkin-Reed-Sternberg (HRS) cells are in a minority, being greatly outnumbered by nonneoplastic cells such as lymphocytes, macrophages, eosinophils, mast cells, fibroblasts, microvessels and other stromal elements. In recent years this microenvironment, largely recruited by the HRS cells through the secretion of a variety of chemokines and cytokines, has been shown to play an essential role in pathogenesis [2,3]. An increased number of FOXP3+ regulatory T cells (Tregs) has been related to better outcome and longer survival [4,6]
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