Collagen VI deposition mediates stromal T cell trapping through inhibition of T cell motility in the prostate tumor microenvironment

Pruitt, Hawley C.; Guan, Yue; Liu, H.; Carey, Alexis; Brennen, W. Nathaniel; Lu, Jiayun; Joshu, Corrine E.; Weeraratna, Ashani T.; Lotan, Tamara L.; Eisinger-Mathason, T.S. Karin; Gerecht, Sharon

doi:10.1016/j.matbio.2023.06.002

Cited by 10 publications

(4 citation statements)

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“…However they were not affected by NgR2 expression in our analysis, although our functional assays show no interaction between αVβ3 and its ligands in the absence of NgR2. This effect may result in increased migration and infiltration in the tumor, or like for Tcells [ 68 ], may just facilitate these cells’ trapping in the prostate TME for local control of the immune response. We therefore suggest that NgR2 is involved in an αVβ3 conformational change leading to its activation state and that this NgR2/active αVβ3 complex may have a role in PrCa reprogramming towards a NE phenotype.…”

Section: Discussionmentioning

confidence: 99%

Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer

Testa,

Quaglia,

Naranjo

et al. 2023

Matrix Biology

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Section: Discussionmentioning

confidence: 99%

Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer

Testa,

Quaglia,

Naranjo

et al. 2023

Matrix Biology

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“…COL4A1 accelerates liver cancer progression, while XVII collagen drives metabolic reprogramming in lung cancer ( Wang et al, 2020 ; Hsu et al, 2020 ). In urological tumors, Collagen VI can not only promote the proliferation and invasion of bladder cancer, but also cause integrin α1-deficient CD4 + T cells to accumulate in the prostate tumor stroma, thereby inhibiting anti-tumor T cell responses ( Piao et al, 2021 ; Pruitt et al, 2023 ). However, there is currently an inadequate comprehension of the relationship between collagen and the heterogeneity of the tumor microenvironment in ccRCC.…”

Section: Introductionmentioning

confidence: 99%

Identification of molecular subtypes and diagnostic model in clear cell renal cell carcinoma based on collagen-related genes may predict the response of immunotherapy

Hong,

Lv,

Xing

et al. 2024

Front. Pharmacol.

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Background: Collagen represents a prominent constituent of the tumor’s extracellular matrix (ECM). Nonetheless, its correlation with the molecular subtype attributes of clear cell renal cell carcinoma (ccRCC) remains elusive. Our objective is to delineate collagen-associated molecular subtypes and further construct diagnostic model, offering insights conducive to the precise selection of ccRCC patients for immunotherapeutic interventions.Methods: We performed unsupervised non-negative matrix factorization (NMF) analysis on TCGA-KIRC samples, utilizing a set of 33 collagen-related differentially expressed genes (33CRDs) for clustering. Our analysis encompassed evaluations of subtype-associated differences in pathways, immune profiles, and somatic mutations. Through weighted gene co-expression network analysis (WGCNA) and four machine learning algorithms, two core genes were found and a diagnostic model was constructed. This was subsequently validated in a clinical immunotherapy cohort. Single cell sequencing analysis and experiments demonstrated the role of core genes in ccRCC. Finally, we also analyzed the roles of MMP9 and SCGN in pan-cancer.Results: We described two novel collagen related molecular subtypes in ccRCC, designated subtype 1 and subtype 2. Compared with subtype 1, subtype 2 showed more infiltration of immune components, but had a higher TIDE (tumor immunedysfunctionandexclusion) score and increased levels of immune checkpoint molecules. Furthermore, reduced prognosis for subtype 2 was a consistent finding in both high and low mutation load subgroups. MMP9 and SCGN were identified as key genes for distinguishing subtype 1 and subtype 2. The diagnostic model based on them could better distinguish the subtype of patients, and the differentiated patients had different progression free survival (PFS) in the clinical immunotherapy cohort. MMP9 was predominantly expressed in macrophages and has been extensively documented in the literature. Meanwhile, SCGN, which was overexpressed in tumor cells, underwent experimental validation, emphasizing its role in ccRCC. In various cancers, MMP9 and SCGN were associated with immune-related molecules and immune cells.Conclusion: Our study identifies two collagen-related molecular subtypes of ccRCC and constructs a diagnostic model to help select appropriate patients for immunotherapy.

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“…Interestingly, these features are also observed in high-grade, poorly differentiated epithelial tumors where they are linked to progression, therapeutic resistance, and poor clinical outcomes (7). Recent studies have shown that the ECM facilitates cancer progression in part by inhibiting T cell migration/infiltration (8)(9)(10)(11). However, the roles of individual ECM proteins in this process are only beginning to be defined.…”

Section: Introductionmentioning

confidence: 99%