Targeted mechanical forces enhance the effects of tumor immunotherapy by regulating immune cells in the tumor microenvironment

Zhu, Pengfei; Lu, Hongrui; Wang, Mingxing; Chen, Ke; Chen, Zheling; Liu, Yang

doi:10.20892/j.issn.2095-3941.2022.0491

Cited by 18 publications

(9 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The main ECM feature common to different tumor types is ECM stiffness, which highly impacts on immune cell infiltration representing a structural and physical barrier to the recruitment of effector T cells. An extreme matrix density and rigidity is also known to associate with impaired drug delivery to the tumors, thus pinpointing ECM stiffness as a double-edge sword deeply impaction on the efficacy of ICI ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Fejza,

Carobolante,

Poletto

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

IntroductionImmune-checkpoint inhibitors (ICIs) have emerged as a core pillar of cancer therapy as single agents or in combination regimens both in adults and children. Unfortunately, ICIs provide a long-lasting therapeutic effect in only one third of the patients. Thus, the search for predictive biomarkers of responsiveness to ICIs remains an urgent clinical need. The efficacy of ICIs treatments is strongly affected not only by the specific characteristics of cancer cells and the levels of immune checkpoint ligands, but also by other components of the tumor microenvironment, among which the extracellular matrix (ECM) is emerging as key player. With the aim to comprehensively describe the relation between ECM and ICIs’ efficacy in cancer patients, the present review systematically evaluated the current literature regarding ECM remodeling in association with immunotherapeutic approaches.MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022351180). PubMed, Web of Science, and Scopus databases were comprehensively searched from inception to January 2023. Titles, abstracts and full text screening was performed to exclude non eligible articles. The risk of bias was assessed using the QUADAS-2 tool.ResultsAfter employing relevant MeSH and key terms, we identified a total of 5070 studies. Among them, 2540 duplicates, 1521 reviews or commentaries were found and excluded. Following title and abstract screening, the full text was analyzed, and 47 studies meeting the eligibility criteria were retained. The studies included in this systematic review comprehensively recapitulate the latest observations associating changes of the ECM composition following remodeling with the traits of the tumor immune cell infiltration. The present study provides for the first time a broad view of the tight association between ECM molecules and ICIs efficacy in different tumor types, highlighting the importance of ECM-derived proteolytic products as promising liquid biopsy-based biomarkers to predict the efficacy of ICIs.ConclusionECM remodeling has an important impact on the immune traits of different tumor types. Increasing evidence pinpoint at ECM-derived molecules as putative biomarkers to identify the patients that would most likely benefit from ICIs treatments.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351180, identifier CRD42022351180.

show abstract

Section: Discussionmentioning

confidence: 99%

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Fejza,

Carobolante,

Poletto

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Increased fibrillar collagen density and radial alignment of collagen are observed in invasive breast tumors and observed in physiologically normal breast involution and in PPBC ( 169 – 171 ). These ECM-based mechanisms inherently improve the motility and invasiveness of breast cancer cells, however, there are also well-documented interactions between ECM dynamics and the immune system, suggesting further downstream effects of the local mechanical involution environment ( 172 , 173 ). Beyond ECM dynamics, there is a distinct role for direct mechanical forces in regulating involution.…”

Section: Biomarkers For Screening/diagnosis Of Postpartum Breast Cancermentioning

confidence: 99%

Status of breast cancer detection in young women and potential of liquid biopsy

Stibbards-Lyle,

Malinovska,

Badawy

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

Young onset breast cancer (YOBC) is an increasing demographic with unique biology, limited screening, and poor outcomes. Further, women with postpartum breast cancers (PPBCs), cancers occurring up to 10 years after childbirth, have worse outcomes than other young breast cancer patients matched for tumor stage and subtype. Early-stage detection of YOBC is critical for improving outcomes. However, most young women (under 45) do not meet current age guidelines for routine mammographic screening and are thus an underserved population. Other challenges to early detection in this population include reduced performance of standard of care mammography and reduced awareness. Women often face significant barriers in accessing health care during the postpartum period and disadvantaged communities face compounding barriers due to systemic health care inequities. Blood tests and liquid biopsies targeting early detection may provide an attractive option to help address these challenges. Test development in this area includes understanding of the unique biology involved in YOBC and in particular PPBCs that tend to be more aggressive and deadly. In this review, we will present the status of breast cancer screening and detection in young women, provide a summary of some unique biological features of YOBC, and discuss the potential for blood tests and liquid biopsy platforms to address current shortcomings in timely, equitable detection.

show abstract

“…To further feed this fertile soil, cancer cells secrete soluble factors like chemokines, cytokines, and growth factors to actively recruit diverse cell types to the TME and reprogram them ( Mao et al, 2021 ). In turn, these cells in the TME facilitate the invasion and migration of cancer cells, their evasion from immune destruction, resistance to chemotherapy, and stimulation of angiogenesis, augmenting the tumor aggressiveness ( de Visser and Joyce, 2023 ; Zhu et al, 2023 ). Hence, a complete understanding of how cancer cells interact with their microenvironment is crucial to overcoming current challenges in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer

Ozmen,

Demir,

Ozcan

2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

Enhanced knowledge of the interaction of cancer cells with their environment elucidated the critical role of tumor microenvironment in tumor progression and chemoresistance. Cancer-associated fibroblasts act as the protagonists of the tumor microenvironment, fostering the metastasis, stemness, and chemoresistance of cancer cells and attenuating the anti-cancer immune responses. Gastric cancer is one of the most aggressive cancers in the clinic, refractory to anti-cancer therapies. Growing evidence indicates that cancer-associated fibroblasts are the most prominent risk factors for a poor tumor immune microenvironment and dismal prognosis in gastric cancer. Therefore, targeting cancer-associated fibroblasts may be central to surpassing resistance to conventional chemotherapeutics, molecular-targeted agents, and immunotherapies, improving survival in gastric cancer. However, the heterogeneity in cancer-associated fibroblasts may complicate the development of cancer-associated fibroblast targeting approaches. Although single-cell sequencing studies started dissecting the heterogeneity of cancer-associated fibroblasts, the research community should still answer these questions: “What makes a cancer-associated fibroblast protumorigenic?”; “How do the intracellular signaling and the secretome of different cancer-associated fibroblast subpopulations differ from each other?”; and “Which cancer-associated fibroblast subtypes predominate specific cancer types?”. Unveiling these questions can pave the way for discovering efficient cancer-associated fibroblast targeting strategies. Here, we review current knowledge and perspectives on these questions, focusing on how CAFs induce aggressiveness and therapy resistance in gastric cancer. We also review potential therapeutic approaches to prevent the development and activation of cancer-associated fibroblasts via inhibition of CAF inducers and CAF markers in cancer.

show abstract

Targeted mechanical forces enhance the effects of tumor immunotherapy by regulating immune cells in the tumor microenvironment

Cited by 18 publications

References 108 publications

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Status of breast cancer detection in young women and potential of liquid biopsy

Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer

Contact Info

Product

Resources

About