A recent study sheds light on the variety of cancer-associated fibroblasts in skin cancers affecting white and black patients, highlighting their distinct roles in modifying the immune response within tumors. The findings might aid in creating new treatments for skin cancer, especially in immunotherapy.
A recent investigation at the Department of Dermatology at MedUni Vienna reveals the variety of cancer-associated fibroblasts in skin cancers affecting individuals of different ethnicities, noting their unique roles in modulating the immune environment within tumors. These findings are crucial for the progression of innovative therapies for skin cancer, particularly in the realm of immunotherapy.
Fibroblasts are specialized cells found in connective tissue, crucial for healing wounds and repairing tissues. They create and organize the extracellular matrix— a network of proteins like collagen that provides tissue strength and flexibility— while also performing several other important functions. Cancer-associated fibroblasts (CAFs) are vital players within solid tumors, significantly impacting cancer progression and the effectiveness of treatments. This study at MedUni Vienna’s Department of Dermatology marks the first exploration into the previously unrecognized diversity of CAFs across different skin cancer types— including basal cell carcinoma, squamous cell carcinoma, and melanoma— using single-cell analysis at both molecular and spatial dimensions.
Through an extensive examination of fibroblasts in their tumor surroundings, and their interactions with other cell types such as epithelial, mesenchymal, and immune cells, researchers identified three distinct subtypes of CAFs: myofibroblast-like RGS5+ CAFs, matrix CAFs (mCAFs), and immunomodulatory CAFs (iCAFs). Notably, the distribution of these subtypes shifts as tumor aggression increases.
Unique subtypes with varied functions in the tumor microenvironment
Among these subtypes, two have the capacity to modulate the immune system, albeit in different manners. mCAFs are known to produce abundant matrix proteins and are usually located at the border between the tumor and the surrounding tissue in less aggressive tumors. They form a barrier that may inhibit immune cells like T cells from penetrating the tumor. Conversely, iCAFs are more prevalent in aggressive skin cancer forms (such as invasive basal cell carcinoma and high-grade melanoma). These cells generate significant amounts of signaling molecules (cytokines and chemokines) that are crucial for attracting and activating immune cells.
“A fascinating finding was that healthy fibroblasts exposed to the secretions of skin cancer cells in a lab setting began to exhibit behavior similar to iCAFs, indicating their ability to activate naïve T cells,” explains study leader Beate Lichtenberger from MedUni Vienna’s Department of Dermatology. “This suggests potential pathways to target these specific subtypes.”
The implications of these findings are substantial for devising new treatments for skin cancer, especially in immunotherapy. Beate Lichtenberger emphasizes the relevance of these results: “By specifically targeting the various CAF subtypes, particularly the immunomodulatory iCAFs, we could significantly enhance treatment effectiveness through improved immune responses and reduced tumor spread. These insights could pave the way for innovative therapy methods, making skin cancer treatments much more efficacious.”
