Each year, more than 300,000 people are diagnosed with melanoma worldwide, and the number is estimated to rise. While mutations in genes like BRAF and NRAS, two of the most common genetic alterations in melanoma, can drive tumor growth, they don’t tell the whole story. Increasingly, research points to the importance of the tumor’s microenvironment—and how melanoma cells interact with their surroundings.

From early-stage tumors to metastatic spread, it’s not just what happens inside a melanoma cell that matters—but how it communicates with those around it.

The Hidden Language of Melanoma

Melanoma cells are in constant conversation with nearby immune cells, fibroblasts, and the extracellular matrix. Through cytokines, extracellular vesicles, and direct receptor–ligand interactions, they reshape their surroundings—contributing to immune suppression, tissue remodeling, and tumor progression. These signaling mechanisms are deeply integrated into how the tumor interacts with its environment and evolves over time (Nanru, 2024).

For example, when melanoma cells interact with immune cells, they can influence the recruitment of tumor-associated macrophages that make it harder for the immune system to respond. These aren’t isolated events, but part of a larger network of communication that sustains the disease. It is well established  that immune checkpoint pathways, such as PD-1 and PD-L1, play an important role in shaping the melanoma microenvironment (Zillberg et al., 2025).

Why It Matters

Melanoma’s ability to manipulate cell-cell communication is one reason it can be so resistant to treatment. Understanding these conversations between melanoma cells, immune cells, and stromal cells can reveal why certain therapies fall short. It’s also why melanoma became a proving ground for immunotherapy: its complex, highly active signaling networks are both a challenge and an opportunity.

Recent research in spatial proteomics has emphasized that these signaling dynamics are not just molecular—but spatially organized in ways that affect therapeutic outcomes (Bungaro et al., 2025).

By mapping these interactions, researchers can uncover new insights into how the tumor microenvironment functions—and identify patterns that may inform future research or treatment strategies.

What We’re Doing at Moleculent

At Moleculent, we’re developing tools to map cellular interactions in complex tissue environments. Our technology helps researchers map how melanoma cells communicate with their surroundings through ligand-receptor interactions. This gives a clearer picture of how melanoma adapts, resists, and spreads. By uncovering these patterns, we aim to support both a deeper understanding of melanoma and the development of therapies that reflect its full biological complexity.

Looking ahead

As research moves beyond the genome toward understanding tumor ecosystems, the ability to map how cells interact will be essential. With the right tools, we can uncover insights that were previously out of reach.

References:

  1. Nanru P. Immunomodulatory effects of immune cell-derived extracellular vesicles in melanoma. Frontiers in Immunology. Frontiers (2024) doi:10.3389/fimmu.2024.1442573
  2. Zillberg F, et al. The tumor immune microenvironment in primary cutaneous melanoma. Virchows Archiv. Springer (2025). doi:10.1007/s00403-024-03758-8
  3. Bungaro C, Guida M, Apollonio B. Spatial proteomics of the tumor microenvironment in melanoma: current insights and future directions. Frontiers in Immunology. Frontiers (2025). doi:10.3389/fimmu.2025.1568456