PhD Scientific Days 2024

Poster Session J - Pathological and Oncological Sciences 1.

Intercellular Communication and CD8+ T-cell Trajectory Analysis in Ovarian Cancer Tissues

Text of the abstract

Introduction: Intercellular interactions play a pivotal role in the development, progression, and treatment response of cancer. Single-cell gene expression data can provide insights into cell-cell communication, enabling us to understand the interaction between cancer cells and microenvironmental cells. Understanding these interactions is crucial for uncovering novel therapeutic targets and developing immunotherapy approaches.

Aims: Our aim was to unravel how intercellular communication influences immune cells such as CD8+ T cells in tumors from ovarian cancer patients and identify potential therapeutic targets using single-cell gene expression data.

Method: We pre-processed and integrated 23 ovarian cancer scRNA-Seq samples from four Gene Expression Omnibus datasets. We delineated distinct cellular populations based on the expression patterns of genes differentially expressed in each cluster and based on canonical marker genes used in previous studies. Then, we performed a pseudotime trajectory analysis of CD8+ T cell subtypes and studied their communication with ovarian cancer cells. Analysis was done in R using Seurat, Monocle3, and CellChat.

Results: Investigating cell lineage and inferring pseudotimes with trajectory analysis revealed the transition of the CD8+ T cells from naïve-like to six different end-states. We found that ovarian cancer cells had stronger communication with central memory cells, terminally differentiated effector memory cells, terminally precursor exhausted cells, and terminally exhausted cells via midkine signaling pathway through MDK-NCL ligand-receptor interactions. In the macrophage-initiation inhibitory factor pathway network, we found stronger interaction of ovarian cancer cells with effector memory cells through MIF-(CD74+CXCR4) ligand-receptor interactions. Our results also revealed that in the collagen and laminin signaling pathway network, ovarian cancer cells expressing COL1A1 and LAMC1 ligands had stronger interaction with naïve cells and central memory cells expressing receptor CD44.

Conclusion: The communication hubs and ligand-receptor pairs identified in our analysis can serve as therapy targets for a new generation of adjuvant therapy designed to suppress tumor cell influence on the microenvironment and to enhance immunotherapy efficiency.