Research

Life Sciences & Biotechnology

Title :

Elucidating the Role of Systemic Immune Responses in Metastasis using Single Cell RNA Sequencing: Relation with Circulating Tumour Cell Biology and Clinical Implications

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. Arindam Maitra, National Institute Of Biomedical Genomics, West-Bengal

Timeline Start Year :

2023

Timeline End Year :

2026

Contact info :

Details

Executive Summary :

The understanding of the interplay between tumor cells and host immune cells has grown in the last two decades due to advancements in cell biology. However, routine approaches like bulk RNAseq cannot decipher the single cell level interactions between tumor cells and host immune system cells. Exponential strategies like single cell RNAseq can help usher in new horizons for biological interplay. A collaborative strategy between PGIMER and NIBMG aims to establish this strategy. Metastasis accounts for 90% of cancer-associated deaths, with tumor cells (CTCs) being key players in the process. Immune evasion and modulation of peripheral immune responses beyond the local tumor micro-environment are critical steps in the development of metastases. The study observed that HNSCC patients with similar tumor staging and grading had different CTC status. The hypothesis is that most patients have CTCs released in the blood but immune cells clear them off from circulation, while others efficiently evade the immune system, leading to differential CTC status and potentially different outcomes. The proposal proposes using Single Cell Sequencing as a model exponential technology to discover the role of immune cells in the presence of CTCs in circulation, which can be a marker for molecular metastasis. The first objective is to perform Single Cell RNA sequencing of immune cells isolated from CTC-positive and CTC-negative patients, detecting differences in cell type diversities, relative abundance, cell states, and gene expression programs. The second objective is to validate different gene expression programs identified in different immune cells using qRT-PCR. The third objective is to estimate various cytokines in serum and compare them between CTC positive and negative patients to explore the role of systemic inflammation in CTC status.

Co-PI:

Dr. Nidhan K Biswas, National Institute Of Biomedical Genomics, West-Bengal-741251, Dr. Arnab Pal, Post Graduate Institute Of Medical Education And Research (PGIMER) Chandigarh-160012, Dr. Sushmita Ghoshal, Post Graduate Institute Of Medical Education And Research (PGIMER) Chandigarh-160012, Prof. Jaimanti Bakshi, Post Graduate Institute Of Medical Education And Research (PGIMER) Chandigarh-160012, Dr. Debajyoti Chatterjee, Post Graduate Institute Of Medical Education And Research (PGIMER) Chandigarh-160012

Total Budget (INR):

70,53,840

Organizations involved