Lrrc15, the leucine-rich repeat-containing protein 15, is involved in cell-cell and cell-matrix interactions. It is expressed on stromal fibroblasts in many solid tumors and directly on some cancer cells of mesenchymal origin. LRRC15 expression can be induced by TGFβ on activated fibroblasts and mesenchymal stem cells [3]. It has been implicated in multiple biological processes related to cancer and virus-host interactions.

In cancer, genetic mouse models have provided insights into its role. Using Lrrc15-diphtheria toxin receptor knock-in mice to selectively deplete LRRC15+ cancer-associated fibroblasts (CAFs) in pancreatic cancer mouse models, it was found that this depletion reduced the total tumour fibroblast content, recalibrated the CAF composition, relieved the suppression of tumour-infiltrating CD8+ T cells, and enhanced their effector function, leading to tumour regression in response to anti-PDL1 immune checkpoint blockade [2]. In ovarian cancer, complementary models demonstrated that LRRC15 promotes metastasis by inhibiting anoikis-induced cell death, promoting adhesion and invasion, and interacting with β1-integrin to stimulate focal adhesion kinase (FAK) signaling. Targeting LRRC15 with the antibody-drug conjugate ABBV-085 prevented metastatic dissemination in xenograft models [1].

In conclusion, Lrrc15 plays a significant role in cancer development and metastasis, especially in promoting tumour-fibroblast interactions and cancer cell metastasis. The use of gene-targeted mouse models, such as Lrrc15-related knockout models, has revealed its role in the tumour microenvironment and response to immunotherapy, providing potential therapeutic targets for cancer treatment [1,2]. Additionally, it also has functions in regulating SARS-CoV-2 entry, which further broadens its significance in biomedical research [4,5].