Prognostic impact of CD163 and CD11c in B cell lymphomas

Abstract

Diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) are aggressive non-Hodgkin lymphomas often diagnosed at advanced stages in elderly patients. Current tools for patient stratification do not sufficiently identify patient groups resistant to treatment. The presence of CD11c+ cells has previously been associated with pro-inflammatory tumour-immune microenvironment (TIME), while CD163+ cells have been linked to anti-inflammatory TIME. This study investigates the correlation between CD11c+ and CD163+ cells and overall survival (OS) in DLBCL and MCL patients from the BLISS cohort. Tissue cores from biopsies were immunofluorescently stained, imaged, and the cells were classified. High frequency of CD11c+ cells was found to correlate with better OS for both DLBCL and MCL, while high frequency of CD163+ cells correlated with shorter OS in MCL but not in DLBCL. The difference remained significant even when adjusted for p53 overexpression and age at diagnosis. Furthermore, frequency of CD11c+ and CD163+ cells was independent of the international diagnostic indices IPI and MIPI, and high CD11c and CD163 expression was mutually exclusive in DLBCL but not MCL. The findings are largely consistent with previous research, and suggest CD11c and CD163 could be useful as both a prognostic marker and a new TIME-modifying therapeutic target. However, more studies are necessary to gain better understanding of the spatial distribution of CD11c+ and CD163+ cells.

Popular Abstract

Non-Hodgkin lymphomas are the 10th most common group of cancers world-wide, with around half a million new cases diagnosed every year. They are a group of blood cancers that develop from a type of immune cells called lymphocytes, including B cells, the cells that produce antibodies. B-cell lymphomas are most often treated by a combination of chemotherapy drugs and an antibody drug, where the antibody is specifically designed to bind to a marker present only on the cancerous B cells. This antibody works in several ways, but most importantly it helps the body's immune system recognize and kill the cancer cells. Still, many patients either don't respond to this treatment at all, or get better initially but relapse later. It is therefore necessary to find new ways of predicting how a given individual will respond to treatment, and to find new targets for cancer therapies. This can be done by studying the cancer cells themselves and identifying what abnormalities they contain and what markers are present on their surface, but recently it was also proven that it is useful to study other cells close to the tumour. The cancer cells themselves and the immune cells in between and around them together form a complex network, called the tumour-immune microenvironment. In this environment, small changes in the crosstalk between the cells can have a big influence on the ability of the immune cells to react to the cancer. If we could design a drug that could sway the crosstalk in the right way, it could be a massive help in getting the immune cells to become active and kill the cancerous B cells. To do this, we first need to understand how the microenvironment works and how it relates to patient outcomes.
In this project, we investigated whether two molecular markers present on immune cells can be linked to a difference in survival for two types of non-Hodgkin lymphomas. The first marker, CD11c, is often present on immune cells that send out inflammatory signals, helping the other cells in the surrounding area become active, recognize the cancer cells, and kill them. On the other hand, cells that have the second one, CD163, often send out signals meant to suppress the immune response. While this can be useful to e.g. prevent the body from overreacting to non-dangerous substances like pollen or peanuts, in the case of cancer it prevents other cells from effectively killing the cancer cells. We found that in the two examined cancer types, patients with a large number of cells that have CD11c on their surface generally live longer than those with fewer cells with CD11c. In one of the cancer types, we could also see that patients with a large number of cells with CD163 on their surface generally lived shorter, but for the other cancer type the same difference could not be seen. Similar patterns have previously been seen in other cancer types as well. In the future, it could be possible to use this information to design a drug that e.g. prevents the cells with CD163 present on their surface from sending out suppressive signals to the other immune cells in the area, or a drug that helps immune cells transition from the immune-suppressive state to the inflammatory one.

• author: Janská, Anna
• supervisor: Sara Ek; Angelica Johansson
• organization: Department of Immunotechnology
• course: KIMM05 20241
• year: 2024
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 9163516
• date added to LUP: 2024-06-18 11:32:38
• date last changed: 2024-06-18 11:32:38