Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy

Liu, Yao; Xun, Zhenzhen; Ma, Kai-Kuang; Liang, Shuhang; Li, Xianying; Zhou, Shaojun; Sun, Li; Liu, Yufeng; Du, Yanhua; Guo, Xinyu; Cui, Tianming; Zhou, Huanran; Wang, Jizhou; Yin, Dalong; Song, Ran; Zhang, Shugeng; Cai, Wei; Meng, Fanzheng; Guo, Hongrui; Zhang, Bo; Yang, Di; Bao, Rujuan; Hu, Qingsong; Wang, Jiabei; Ye, Youqiong; Liu, Lianxin

doi:10.1016/j.jhep.2023.01.011

Cited by 233 publications

(162 citation statements)

References 35 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…In addition, it further revealed that the crosstalk between SPP1 + macrophages and CAFs contributed to ECM remodeling and TIB formation, which led to reducing immune infiltration in the tumor tissue. Moreover, in vivo experiments have verified that SPP1 inhibition in mice with liver cancer resulted in better immunotherapy efficacy with anti-PD-1 (111). Although the molecular mechanism of SPP1-mediated crosstalk between SPP1 + macrophages and CAFs is not completely clear and the role of the crosstalk between SPP1 + macrophages and CAFs has not been verified in clinical trials, SPP1-blockading is promising for improving the efficacy of HCC treatment with ICIs.…”

Section: Mediums or Means Resultsmentioning

confidence: 99%

“…A lot of previous researches centered on linking various cells in TME with immunotherapy effectiveness. The latest study indicated that TME subtypes of HCC are associated to the immunotherapy efficacy by combining spatial transcriptomics with single-cell RNA sequencing (scRNA-seq) and multiplexed immunofluorescence of anti-PD-1-treated HCC patients ( 111 ). It suggested that the tumor immune barrier (TIB) structure consisting of SPP1 + macrophages and CAFs near the tumor boundary affected the therapeutic efficacy of ICIs.…”

Section: The Roles Of Cafs or Hscs In Cellular Crosstalkmentioning

confidence: 99%

“…For example, it has been revealed that a metabolic network-driven approach can stratify the HCC tumors into three distinct tumor subtypes ( 154 ). The latest study has revealed that TME subtypes of HCC are associated with the immunotherapy efficacy ( 111 ). Therefore, researching the structures of TME subtypes in categories and exploring the molecular mechanisms of cellular crosstalk based on that are expected in the future for the development of precision medicine.…”

Section: Conclusion and Expectationmentioning

confidence: 99%

See 2 more Smart Citations

A key driver to promote HCC: Cellular crosstalk in tumor microenvironment

et al. 2023

View full text Add to dashboard Cite

Liver cancer is the third greatest cause of cancer-related mortality, which of the major pathological type is hepatocellular carcinoma (HCC) accounting for more than 90%. HCC is characterized by high mortality and is predisposed to metastasis and relapse, leading to a low five-year survival rate and poor clinical prognosis. Numerous crosstalk among tumor parenchymal cells, anti-tumor cells, stroma cells, and immunosuppressive cells contributes to the immunosuppressive tumor microenvironment (TME), in which the function and frequency of anti-tumor cells are reduced with that of associated pro-tumor cells increasing, accordingly resulting in tumor malignant progression. Indeed, sorting out and understanding the signaling pathways and molecular mechanisms of cellular crosstalk in TME is crucial to discover more key targets and specific biomarkers, so that develop more efficient methods for early diagnosis and individualized treatment of liver cancer. This piece of writing offers insight into the recent advances in HCC-TME and reviews various mechanisms that promote HCC malignant progression from the perspective of mutual crosstalk among different types of cells in TME, aiming to assist in identifying the possible research directions and methods in the future for discovering new targets that could prevent HCC malignant progression.

show abstract

Section: Mediums or Means Resultsmentioning

confidence: 99%

Section: The Roles Of Cafs or Hscs In Cellular Crosstalkmentioning

confidence: 99%

Section: Conclusion and Expectationmentioning

confidence: 99%

See 1 more Smart Citation

A key driver to promote HCC: Cellular crosstalk in tumor microenvironment

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Single-cell analysis in breast cancer has also shown that SPP1-positive TAMs express high levels of apolipoprotein E (APOE), CD204, CD68, and CADM1. High densities of SPP1-expressing TAMs and CAF appear associated with resistance to immunotherapy in hepatocellular carcinoma, and animal studies have revealed that SPP1 secreted from TAMs is involved in the infiltration of CAFs and suppression of CTL infiltration into tumor tissues [ 92 ]. Cancer stem cells of gastric cancer expressed high levels of CD44 [ 93 ].…”

Section: Significance Of Spp1 Expression In Tams In Malignant Tumors ...mentioning

confidence: 99%

The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages

Matsubara

Yano

Pan

et al. 2023

Cancers

View full text Add to dashboard Cite

Macrophages are a representative cell type in the tumor microenvironment. Macrophages that infiltrate the cancer microenvironment are referred to as tumor-associated macrophages (TAMs). TAMs exhibit protumor functions related to invasion, metastasis, and immunosuppression, and an increased density of TAMs is associated with a poor clinical course in many cancers. Phosphoprotein 1 (SPP1), also known as osteopontin, is a multifunctional secreted phosphorylated glycoprotein. Although SPP1 is produced in a variety of organs, at the cellular level, it is expressed on only a few cell types, such as osteoblasts, fibroblasts, macrophages, dendritic cells, lymphoid cells, and mononuclear cells. SPP1 is also expressed by cancer cells, and previous studies have demonstrated correlations between levels of circulating SPP1 and/or increased SPP1 expression on tumor cells and poor prognosis in many types of cancer. We recently revealed that SPP1 expression on TAMs is correlated with poor prognosis and chemoresistance in lung adenocarcinoma. In this review, we summarize the significance of TAMs in lung cancers and discuss the importance of SPP1 as a new marker for the protumor subpopulation of monocyte-derived TAMs in lung adenocarcinoma. Several studies have shown that the SPP1/CD44 axis contribute to cancer chemoresistance in solid cancers, so the SPP1/CD44 axis may represent one of the most critical mechanisms for cell-to-cell communication between cancer cells and TAMs.

show abstract

“…Numerous studies have investigated the application of T cells in anti-tumor immunotherapies [8][9][10]. Nonetheless, the immunosuppressive tumor microenvironment (TME) in solid tumors, such as OSCC, continues to be a therapeutic barrier for current immunotherapy strategies [11,12]. In general, tumorassociated macrophages (TAMs), the most prevalent immune cells in ltrating in TEM, are a substantial component of the immune microenvironment and play an indispensable role in the body's innate immunity and acquired immunity [13,14].…”

Section: Introductionmentioning

confidence: 99%

Single-cell transcriptome and TCR profiling revealed the immunosuppression caused by Macrophages and T cells in the chemoresistant oral tongue squamous cell carcinoma

Song

Sun

et al. 2023

Preprint

View full text Add to dashboard Cite

Background After surgical treatment, chemotherapy is one of the most common strategies for advanced oral squamous cell carcinoma (OSCC). The majority of patients, especially those with advanced OSCC of the tongue, are refractory to chemotherapy or have acquired resistance, and the underlying mechanism remains unknown. Methods The transcriptomes of 62,375 single cells from 15 samples (14 primary OTSCC (PT, n = 13), recurrent OTSCC (RT, n = 1), and normal tongue tissue (NT, n = 1) were analyzed. The recurrent OTSCC tissue was obtained from the patient who has received a combination of chemotherapeutic drugs for the past four years since the initial surgery in 2018. Additionally, TCR sequencing was undertaken on three samples (RT, PT, and NT; n = 1 each). The composition, purpose, and lineage relationship of macrophage and T lymphocytes within three different groups were then determined using an integrative analysis. Results We observed a greater infiltration of immune cells in recurrent OTSCC than in primary OTSCC, as indicated by the accumulation of dysfunctional cytotoxic CD8 + T cells and macrophages. As indicated by the distinct distribution and functions of C1Qs + and SPP1 + tumor-associated macrophages, respectively, macrophages in PT exhibited pro-tumor and anti-inflammatory effects, whereas macrophages in RT showed greater non-polarization. In addition, we identified a substantial population of CD8 + T cells in RT patients that exhibited a continuous transition from regulatory to cytotoxic T cells. In addition, we identified two clusters of substantially increased cytotoxic CD8 + T cells and regulatory CD4 + T cells in RT patients. The interaction between macrophages and T cells was evaluated lastly. We found that SPP1 and MIF may be responsible for immunosuppression in the microenvironment of OTSCC tumors following long-term chemotherapy. Conclusion Long-term chemotherapy induced distinct OTSCC tumor microenvironment transcriptomes, particularly immunosuppression in recurrent tumors, which may correlate with tumor chemoresistance.

show abstract

Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy

Cited by 233 publications

References 35 publications

A key driver to promote HCC: Cellular crosstalk in tumor microenvironment

A key driver to promote HCC: Cellular crosstalk in tumor microenvironment

The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages

Single-cell transcriptome and TCR profiling revealed the immunosuppression caused by Macrophages and T cells in the chemoresistant oral tongue squamous cell carcinoma

Contact Info

Product

Resources

About