Two clinically opposing CAF subsets a favorable subset (PI16+/SLIT2+/ADAM28+), enriched in responders (CR/PR), regulating cell differentiation and immunoregulation as well as a tumor-promoting subset (BMP4+/FAP+/MMP1+), enriched in non-responders (NR), upregulating collagens, matrix metalloproteinases (MMPs), and WNT signaling to drive ECM remodeling and progression. Here, PI16 is linked to neoplasm.