Anna Nikkarinen: From Macrophages to Mutations: Tumour Microenvironment and Genetic Evolution in Mantle Cell Lymphoma

Abstract

Mantle Cell Lymphoma (MCL) is, despite recent advances, still not considered curable. The aim of this thesis is to increase the understanding of MCL tumour biology by describing the impact of the immune microenvironment and tumour genetics on the outcome for the patient.

In a first study (paper I) we described the composition of the tumour immune microenvironment in MCL tumour tissue. We found that CD3+ T-cells were the most abundant cell type in the tumour tissue, and that high numbers of FOXP3+ regulatory T-cells and CD163+ macrophages were associated with shorter survival.

The negative prognostic impact of macrophages in MCL was confirmed in a second study (paper II) where we investigated the soluble macrophage marker sCD163 and found that high serum levels correlated with worse prognosis in both newly diagnosed and relapsed MCL patients. 

The third study (paper III) further underscores the importance of macrophages in MCL. In this study, we analysed differences in the plasma proteome between patients that did or did not relapse before 24 months (POD24). Among 1463 proteins, the most differentially expressed were two macrophage markers, sCD169 and sVSIG4. 

In the fourth study (paper IV) we focused on tumour genetics, using sequential tumour biopsies. We showed that MCL tumours accumulate high-risk genetic alterations over time, and that the type of treatment the patient received affected the risk of developing such alterations.

Treatment is also the focus of the last study (paper V), where we described a higher risk of acute haematologic side effects in patients with clonal haematopoiesis. 

In summary, this thesis has provided new insights about the tumour microenvironment in MCL and advanced the understanding of how anti-tumour treatments interact with tumour biology as well as with patient intrinsic factors.