Tumor Microenvironment—Current Status and Therapeutic Targets

Dear Colleagues,

The tumor microenvironment (TME) refers to the complex and dynamic ecosystem surrounding tumor cells, comprising immune cells, fibroblasts, endothelial cells, the extracellular matrix (ECM), signaling molecules, and blood vessels. This environment plays a pivotal role in cancer initiation, progression, immune evasion, and resistance to therapies. Recent research has shown that the TME not only supports tumor growth but also suppresses effective antitumor immune responses. Key components such as tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs) create an immunosuppressive milieu. Hypoxia, low pH, and abnormal vasculature within the TME further enhance tumor survival and metastasis.

Therapeutic strategies targeting the TME are gaining traction, and include the following:

• Immune checkpoint inhibitors (e.g., anti-PD-1, anti-CTLA-4) to restore T-cell activity.
• Modulation of TAMs and CAFs to reprogram the immune response.
• Antiangiogenic agents (e.g., bevacizumab) to normalize tumor vasculature.
• Targeting metabolic pathways to disrupt the supportive environment of tumors.
• Nanoparticle delivery systems for targeted drug delivery within the TME.

The TME remains a promising but complex target. Combining TME-targeted therapies with conventional treatments like chemotherapy, radiotherapy, and immunotherapy is a current focus of translational research, aiming to overcome therapeutic resistance and improve patient outcomes.
In this Special Issue, we invite manuscripts that explore various cancer subtypes, with a focus on harnessing the tumor microenvironment to develop innovative therapeutic strategies.

Dr. Rashi Kalra
Guest Editor

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