Inflammation and lymphoma: Therapeutic implications

A variety of therapeutic targets are emerging from studies investigating the lymphoma microenvironment. However, the translation of our current knowledge of tumor microenvironment into hypothesis-driven clinical trials remains a challenging issue. Targeting the microenvironment in order to obtain a potent antitumor activity with biological drugs combined with conventional therapy is an intriguing working hypothesis that has to face a variety of obstacles andmechanisms of resistance. The inherent complexity of mechanisms regulating growth, proliferation and survival of lymphoma cells, along with differences in pathway(s) activation, differences in the cellular composition of the microenvironment in patients with the same histological diagnosis, as well as the ability of lymphoma cells to escape drug-induced damage represent potential explanation for the limited results so far reported in clinical trials with agents targeting non-neoplastic cells. Future efforts will have to be focused on combination therapy with new and standard agents and on developing biomarkers based on microenvironment features. Identifying predictive and prognostic biomarkers related to characteristics of non-neoplastic cells could be a helpful tool in order to optimize the effects of new drugs and overcoming the risk of poor outcome related to inadequate patient selection. On the basis of new knowledges emerging .from preclinical and clinical studies, future trials targeting microenviron- ment and inflammatory infiltrate in lymphoma patients are warranted.