A recent study revealed collagen reorganization in melanoma during immunotherapy, offering new insights for treatment response.

Published in Biophotonics Discovery, investigators quantified in vivo collagen reorganization in C57BL/6 mice bearing intradermal B78 melanoma tumors during immunotherapy using second harmonic generation (SHG) imaging. They examined collagen changes in the preclinical melanoma models treated with a combination of external beam radiation therapy, α-CTLA-4 antibody, and Hu14.18-IL2 immunocytokine.

Increased collagen linearization and deposition during tumor progression can impede immune cell infiltration and promote metastasis, noted investigators. "Although melanoma is well studied in immunotherapy research, studies that quantify collagen changes during melanoma progression and treatment are lacking."

SHG imaging was used to monitor collagen in vivo over the treatment course. The mice were randomized into treatment groups to receive the immunotherapy combination, or a phosphate-buffered saline (PBS) vehicle as a control. Collagen morphology was analyzed by investigators using CurveAlign and CT-FIRE software, assessing both image and single-fiber levels.

The investigators' findings included significant collagen reorganization in treated mice, resulting in shorter, wider, and curlier collagen fibers, with a modest increase in collagen density vs. the PBS mice. Collagen fiber straightness and length changed significantly late in treatment (days 9 and 12), while width and density changed early (day 6). Within the treated group, collagen fibers became significantly curlier and shorter from days 6 to 12. The authors also noted a significant increase in α-SMA+ cancer-associated fibroblasts at day 6 in treated tumors, suggesting their potential role in the observed collagen changes.

"To our knowledge, this is the first study to quantify in vivo mouse melanoma tumor collagen reorganization during immunotherapy treatment using label-free SHG imaging," stated investigators. "During tumorigenesis, cancer cells and CAFs secrete excess MMPs and collagen, which often leads to the reconstruction, linearization, and remodeling of collagen in the tumor microenvironment. This remodeling may be especially relevant for melanoma patients whose skin is 70% collagen and whose tumors are often fibroblast-rich."

The authors declared no conflicts of interest related to this work.