The study by Heaton et al. marks a significant advancement in understanding the role of collagen remodeling within the melanoma tumor microenvironment during immunotherapy. Using in vivo second-harmonic generation imaging, the authors quantitatively tracked dynamic changes in collagen morphology in a preclinical melanoma model, revealing a shift toward a healthier phenotype associated with treatment. These findings enhance our understanding of tumor extracellular matrix dynamics and highlight the potential of optical imaging technologies to guide and optimize cancer immunotherapy. This commentary will explore these findings, contextualize them within the broader field of tumor immunology, and discuss their implications for improving immunotherapy strategies in melanoma and other cancers.

The commentary remarks on recent work that demonstrates the power of multimodal, label-free imaging to elucidate radiation resistance mechanisms and provides a useful method for plotting multivariable imaging data, uncovering metabolic heterogeneity bulk analyses would miss.

The article clarifies a correction to the published article: Column 1 in the third row of Table 2 was corrected to be 47 rather than 22B.

The note clarifies a correction to the published article.