Higher Number of Dendritic Cells and Lower Number of Mast Cells Impact Overall Survival in Mantle Cell Lymphoma
Authors: Kiryakoza Morgan , Sallan Lorin , Hanona Paul , Jairath Neil , Ezekwudo Daniel , Jaiyesimi Ishmael A. 
Published: December 2024

Background: Mantle cell lymphoma (MCL) is named so as it develops in the mantle zone of lymph nodes. Its pathogenesis is thought to be due to cyclin D1 overexpression which leads to unregulated proliferation of cancerous cells. Similarly, the tumor microenvironment plays a large role in the development of malignancy. The tumor microenvironment in lymphomas is a mix of different immune cells, vessels, extracellular matrix, and more. Dendritic cells, an important component of said environment, have a known protective effect in many malignancies. Conversely, mast cells represent a different component with a possible strong association with tumor development. Current treatment for MCL has a wide range, including chemotherapies, gene therapies, and immunotherapies. With further research into the mast cell association with MCL, this represents a potential target for future treatment of MCL.

Methods: This project examines a sample set of 41 patients taken from a publicly available MD Anderson RNA sequencing dataset. RNA sequences were extracted and inputted into CIBERSORT, a Stanford application that identifies the impact different immune cells have on a tumor microenvironment. The immune cells included are B-cells naïve, B-cells memory, plasma cells, CD8 T-cells, CD4 T-cells, T-cells follicular, T-cells regulatory, natural killer activated cells, natural killer resting cells, monocytes, macrophages (M0, M1, M2), activated dendritic cells, resting dendritic cells, activated mast cells, resting mast cells, eosinophils, and neutrophils. CIBERSORT outputs immune cell fractions. These fractions are input into a statistical analysis tool, Radiant by Shiny, that calculates a linear regression that describes the relationship between each immune cell and its impact on overall survival.

Results: Dendritic cells were prognostic of increased survival (p=.030), as evidenced by a positive coefficient of correlation of +4226. In contrast, resting mast cells had a strong, negative impact on overall survival (p = 0.033). The coefficient of correlation was -2146.

Discussion: Results of our analysis revealed the strong and positive relationship that dendritic cells have on overall survival in MCL and the strong negative relationship of mast cells. Dendritic cells likely impart this positive effect through their ability of enacting tumor specific cell killing, thus a higher amount of these cells imparts increased overall survival. In contrast, there are numerous hypotheses into the mechanisms in which mast cells influence and increase tumorigenesis. One such hypothesis suggests that mast cells promote immunosuppression and therefore tumor growth, potentially through cytokine, such as IL-10 and 6 , signaling. Moreover, they may decrease rate of tumor cell death through these same cytokine mechanisms. Mast cells also release numerous factors that promote angiogenesis, an essential component of tumor cell growth. In this way, the mast cell retains a strong role in the tumor microenvironment of lymphomas and increased amounts have a decreased overall survival. Identification of this key player in tumorigenesis offers a potential target of future treatment.