Page 25 - Haematologica August 2018

Immune escape mechanisms in lymphoma
phomas,116 secondary cutaneous DLBCL, primary cuta- neous leg-type DLBCL,70 and HL,117 but seems to be weak in non-aggressive lymphomas (such as small lymphocytic lymphoma, lymphoplasmacytic lymphoma, and grade 1 FL) and MCL.116 In DLBCL, FASL expression is an adverse prognostic marker.69-72
Immunosuppressive microenvironment
Lymphoma cells may evade immune eradication by inducing an immunosuppressive (humoral and cellular) microenvironment. Interactions between the lymphoma cells and their microenvironment have been reviewed in detail by Scott and Gascoyne.118 Here, we highlight the main immunosuppressive components present in the lym- phoma microenvironment (Figure 1, "immunosuppressive microenvironment").
Cytokines
IL-10 secretion
IL-10 is an immunosuppressive cytokine which inhibits myeloid effector cells and priming functions of DC, pro- motes Th2 immune responses, induces Treg, and stimu- lates growth and differentiation of B cells.119 Thus, IL-10 may promote lymphoma in two ways: i) by stimulating the growth of tumor B cells; ii) by inducing an immuno- suppressive environment. IL-10 serum level is higher in lymphoma patients than in healthy subjects and is associ- ated with poor prognosis.120,121 Moreover, high levels of IL- 10 before treatment is associated with treatment failure and a worse outcome.120-122
TGF-b secretion
TGF-b inhibits CTL function and promotes an immuno-
Table 1. Overview of lymphoma immune escape mechanisms. The respective contribution of each immune escape mechanism according to lymphoma subtype.
HL: Hodgkin lymphoma; BL: Burkitt lymphoma; DLBCL: diffuse large B-cell lymphoma; PMBL: primary mediastinal B-cell lymphoma; PTL: primary testicular lymphoma; PCNS: primary central nerv- ous system lymphoma; MCL: mantle cell lymphoma; FL: follicular lymphoma; MZL: marginal zone lymphoma; MALT: mucosal associated lymphoid tissue; PTCL-NOS: primary T-cell lymphoma not otherwise specified; AITL: angio-immunoblastic T-cell lymphoma; ALCL: anaplastic large cell lymphoma; CTCL: cutaneous T-cell lymphoma; MF: mycosis fungoid; SS: Sezary syndrome; ATLL: acute T-cell lymphoma/leukemia; ENKTL: extranodal NK/T lymphoma; MDSC: myeloid-derived suppressor cell; TAM: tumor associated macrophage; APM: antigen processing machinery. °Refers to GILT. °°Refers to HLA-DM. *Refers to mycosis fungoid. #Refers to Sezary syndrome.
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