Date of Award

2-5-2025

Publication Type

Thesis

Degree Name

M.Sc.

Department

Biological Sciences

Keywords

Breast cancer; Innate Lymphoid Cells; NK cells; scRNA-seq

Supervisor

Munir Rahim

Rights

info:eu-repo/semantics/embargoedAccess

Abstract

Innate lymphoid cells (ILCs) are heterogeneous innate immune cells which serve as the first line of defense against infectious agents and tumorigenesis by producing a range of effector cytokines similar to their adaptive immune cell counterparts. Based on their cytolytic capacity, ILCs can broadly be categorized into NK cells and non-NK ILCs. In the context of cancer, NK cells exhibit a robust anti-tumorigenic role, as reported by numerous in vivo and in vitro studies, while studies on non-NK ILCs (ILC1s, ILC2s, ILC3s) show that non-NK ILCs can orchestrate both anti- and pro-tumor responses. My research explores the developmental trajectory and plasticity of peripheral ILCs in the tumor macroenvironment of mammary tumor-bearing mice, primarily in the spleen, peripheral blood, and bone marrow. Single cell RNA sequencing (scRNA-seq) analysis of splenic NK cells and flow cytometric analysis of splenocytes and hematopoietic cells was performed to understand the effects of tumorigenesis on NK cell exhaustion, NK-ILC plasticity, and NK developmental aberrations. scRNA-seq analysis of splenic NK cells reveals a larger population of immature NK cells and non-NK ILC1s along with respective ILC-specific cytokines and transcription factors in tumor-bearing mice than in healthy mice. Parallel flow cytometric analysis on peripheral blood mononuclear cells (PBMCs) from breast cancer patients vs healthy donors revealed a similar decline in NK cell frequency. Flow cytometric analysis of bone marrow cells from healthy vs tumor-bearing mice shows a decline in NK progenitor populations. Together these results demonstrate a systemic perturbation of ILC compartment during mammary tumorigenesis.

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