Tumor Microenvironment in Translational Oncology: Histopathological Biomarkers and Therapeutic Targets

Dear Colleagues,

The tumor microenvironment is now recognized as a dynamic and clinically relevant component of cancer progression rather than a passive background. Interactions among neoplastic cells, stromal cells, immune infiltrates, endothelial and lymphatic compartments, extracellular matrix, and soluble mediators shape invasion, metastatic dissemination, response to therapy, and resistance. In daily clinical practice, many of these processes can be captured using histopathology, immunohistochemistry, digital pathology, and clinicopathological correlation, making the tumor microenvironment a timely bridge between diagnostic pathology, translational oncology, and therapeutic decision-making.

Recent advances have highlighted the prognostic and predictive value of microenvironmental features such as tumor budding, the invasive tumor front, cancer-associated fibroblasts, tumor-associated macrophages, mast cells, angiogenesis, lymphangiogenesis, immune exclusion, and spatial immune organization. At the same time, important challenges remain around the standardization of scoring systems, integration of tissue biomarkers into clinically useful models, validation in well-annotated cohorts, and identification of actionable microenvironmental vulnerabilities. Contributions to this Special Issue should therefore emphasize translational and clinically oriented aspects rather than pure molecular transformation mechanisms alone.

This Special Issue aims to present and disseminate the most recent advances related to the tumor microenvironment as a diagnostic, prognostic, predictive, and therapeutic target in human cancer. We welcome original research articles, clinically relevant translational studies, systematic reviews, narrative reviews, and methodological papers addressing tissue-based biomarkers, microenvironmental scoring, immune and stromal profiling, digital or spatial pathology approaches, and therapeutic implications across solid tumors and hematologic malignancies.

Topics of interest for publication include, but are not limited to, the following:

• Histopathological assessment of the invasive tumor front and tumor budding;
• Cancer-associated fibroblasts, extracellular matrix remodeling, and stromal activation;
• Translational studies linking pathology-based biomarkers with treatment responses and patient outcomes;
• Therapeutic targeting of stromal, immune, vascular, and extracellular matrix components;
• Microenvironment-based prognostic and predictive models for clinical practice;
• Immunohistochemical, digital pathology, and spatial pathology biomarkers of the tumor microenvironment;
• Angiogenesis, lymphangiogenesis, vascular niches, and metastatic dissemination;
• Tumor-associated macrophages, mast cells, lymphocytes, and immune microenvironment phenotypes.

Dr. Valeria Zuccalà
Guest Editor

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