Topic: Genomic and Immune Regulation of the Tumor Microenvironment

The tumor microenvironment has become one of the most active areas of cancer research. Much of our current understanding comes from the rapid development of technologies such as single-cell sequencing, spatial omics, and liquid biopsy. These tools have allowed researchers to move beyond bulk measurements and begin examining tumors as complex ecosystems composed of malignant cells, immune populations, stromal cells, and their dynamic interactions.

Over the past decade, the field has undergone an interesting transition. Early efforts largely focused on identifying molecular signatures associated with prognosis, treatment response, or disease progression. While many of these studies generated useful biomarkers, the biological mechanisms behind these observations often remained unclear. More recently, advances in genomics, immunology, and functional studies have shifted attention toward understanding how genetic alterations shape immune responses, how immune cells remodel the tumor microenvironment, and how these processes ultimately influence clinical outcomes.

At the same time, the field is now moving beyond mechanism for mechanism’s sake. There is increasing recognition that technological innovation, biological understanding, and clinical application should not develop independently. Single-cell and spatial approaches are helping to uncover the cellular and molecular basis of tumor behavior, while cfDNA and other liquid biopsy technologies are bringing these discoveries closer to real-world patient management. The challenge is no longer simply generating more data, but translating mechanistic insights into clinically meaningful strategies for diagnosis, patient stratification, treatment selection, and therapeutic monitoring.

This Special Issue aims to highlight studies that connect these different levels of investigation. We welcome contributions addressing genomic regulation, immune remodeling, metabolic interactions, and cellular communication within the tumor microenvironment, particularly those that combine technological innovation with biological insight and translational relevance.

Topics of interest include, but are not limited to:

● Genomic and epigenomic regulation of the tumor microenvironment;

● Tumor–immune interactions and immune cell reprogramming;

● Single-cell, spatial, and multi-omics approaches;

● Cell-free DNA and liquid biopsy applications;

● Mechanisms of immune evasion and immunotherapy resistance;

● Metabolic regulation within the tumor microenvironment;

● Biomarker discovery and validation;

● Computational and AI-assisted approaches for TME research;

● Precision oncology and mechanism-guided therapeutic strategies.

By bringing together studies spanning technology development, mechanistic investigation, and clinical translation, this Special Issue seeks to provide a platform for research that advances both our understanding of the tumor microenvironment and its application to precision cancer medicine.

Early tumorigenesis, tumor microenvironment (TME), multi-omics, computational oncology, biomarkers, precision oncology