Investigating the Interplay of Natural Killer Cells and Microbiome in Non-Hodgkin's Lymphoma

forthcoming

Natural Killer (NK) cells have a critical role in anti-cancer immunity and recently the influence of the microbiome in cancer immunotherapy was shown. Comprehending the complex interplay between the expression of NK cells ligands involved in immune evasion mechanisms and the microbiome is crucial for achieving immunotherapy success. Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) are two types of Non-Hodgkin Lymphomas (NHL) characterized by accumulating B lymphocytes in lymph nodes, and extranodal sites. DLBCL and FL usually show aggressive and indolent behavior respectively. DLBCL, includes the known subtypes germinal center B-cells (GCB) and activated B-cells (ABC), and, like the DLBCL-GCB subtype, FL have a germinal origin as well. The mechanism involved in the immune-microbiome interplay are not clearly understood, hampering the improvement of therapeutic possibilities. The objective of this study is to reveal the complex interplay between the NK cells and the microbiome in DLBCL and FL patients and harness its therapeutic potential. To achieve this, I will use single-cell RNA sequencing and flow cytometry to analyze the composition of NK cells dissociated from DLBCL and FL samples. Then, I will use correlative analyses to identify the NK ligands/receptors that are more expressed in patients with low diversity and high variability microbiome. Ultimately, I will address the impact of this correlation in the response to immunotherapy. The results will pave the way for patient risk stratification establishment and new treatment options approaches. Conducting this project at the Tumor Stroma Interactions (TSI) group will provide me a solid scientific basis as well as technical development for further progressing my scientific career.