Single Cell RNA Sequencing Analysis of the Immune Microenvironment in Treatment Resistant Esophageal Squamous Cell Carcinoma

• Abhishek Kumar Gupta

  Kalinga University, Naya Raipur, Chhattisgarh, India

• Anand Trivedi

  Kalinga University, Naya Raipur, Chhattisgarh, India

Esophageal squamous cell carcinoma (ESCC) is a very aggressive disease that does not respond to the traditional methods of treatment, including chemotherapy and immunotherapy, and therefore has a low prognosis. Tumor immune microenvironment (TIME) is an important factor that contributes to resistance because it affects the function of immune cells and their interactions with tumor cells. The cellular composition and functional state of the immune microenvironment of the treatment-resistant ESCC were examined in the work by means of single-cell RNA sequencing (scRNA-seq). The populations of immune cells were observed to differ in the event of treatment-resistant and treatment-responsive ESCC. There were more exhausted CD8 + T cells, regulatory T cells (Tregs), and immunosuppressive macrophages in the treatment-resistant group. These cells also had high levels of immune checkpoint markers like PD-1, PD-L1, and CTLA-4, which are identified to play a role in inhibiting effective immune responses. In addition, there was also a metabolic reprogramming of these immune populations with an increased glycolytic activity, which leads to a dysfunction of immune cells and allows tumors to survive. Using gene set enrichment analysis (GSEA), there were a few pathways that were upregulated in the resistant cohort, such as immune checkpoint signaling, inflammatory responses, and metabolism pathways. These observations support the assumption that immune escape and metabolic restructuring are two influential factors in ESCC resistance. The findings indicate that both immune checkpoints and the metabolic reprogramming of immune cells may be combined therapies to provide a promising approach in overcoming treatment resistance in ESCC. The findings need to be validated in future studies with larger patient groups, multi-omics studies, and clinical trials to come up with better treatment options among ESCC patients.

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