Transcriptomic analysis of a transgenic zebrafish hepatocellular carcinoma model reveals a prominent role of immune responses in tumour progression and regression

Zhen Li; Huaien Luo; Caixia Li; Xiaojing Huo; Chuan Yan; Xiaoqian Huang; Muthafar Al-Haddawi; Sinnakaruppan Mathavan; Zhiyuan Gong

doi:10.1002/ijc.28794

Immune Responses Following Locoregional Treatment for Hepatocellular Carcinoma: Possible Roles of Adjuvant Immunotherapy

Pharmaceutics ◽

10.3390/pharmaceutics13091387 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1387

Author(s):

Ji-Won Han ◽

Seung-Kew Yoon

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Responses ◽

Immunomodulatory Effects ◽

Long Term Outcomes ◽

Locoregional Treatment ◽

Adjuvant Immunotherapy ◽

Common Cause ◽

Cell Responses

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.

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Transcriptomic analysis reveals the oncogenic role of S6K1 in hepatocellular carcinoma

Journal of Cancer ◽

10.7150/jca.40726 ◽

2020 ◽

Vol 11 (9) ◽

pp. 2645-2655

Author(s):

Keng Po Lai ◽

Angela Cheung ◽

Cheuk Hin Ho ◽

Nathan Yi-Kan Tam ◽

Jing Woei Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcriptomic Analysis

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Antitumour immune responses

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399403005623 ◽

2003 ◽

Vol 5 (3) ◽

pp. 1-22 ◽

Cited By ~ 8

Author(s):

Roshni Mitra ◽

Sarvjeet Singh ◽

Ashok Khar

Keyword(s):

Immune Response ◽

Immune System ◽

Immune Responses ◽

Tumour Progression ◽

Immune Surveillance ◽

Tumour Cells ◽

Transformed Cells ◽

Therapeutic Modalities ◽

Cancerous Cells

The role of the immune system in combating tumour progression has been studied extensively. The two branches of the immune response – humoral and cell-mediated – act both independently and in concert to combat tumour progression, the success of which depends on the immunogenicity of the tumour cells. The immune system discriminates between transformed cells and normal cells by virtue of the presence of unique antigens on tumour cells. Despite this, the immune system is not always able to detect and kill cancerous cells because neoplasms have also evolved various strategies to escape immune surveillance. Attempts are being made to trigger the immune system into an early and efficient response against malignant cells, and various therapeutic modalities are being developed to enhance the strength of the immune response against tumours. This review aims to elucidate the tumouricidal role of various components of the immune system, including macrophages, lymphocytes, dendritic cells and complement.

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Stromal cell sialylation suppresses T cells in inflammatory tumour microenvironments: A new tumour stromal cell immune checkpoint?

10.1101/2021.06.18.447879 ◽

2021 ◽

Author(s):

Hannah Egan ◽

Oliver Treacy ◽

Kevin Lynch ◽

Niamh A Leonard ◽

Grace O'Malley ◽

...

Keyword(s):

Sialic Acid ◽

Immune Responses ◽

Stromal Cells ◽

Immune Checkpoint ◽

Stromal Cell ◽

Immune Cell ◽

Tumour Progression ◽

Tumour Immunity ◽

Cell Suppression

Immunosuppressive tumour microenvironments (TME) reduce the effectiveness of immune responses in cancer. Non-haematopoietic mesenchymal stromal cells (MSC), the precursor to cancer associated fibroblasts (CAFs), dictate tumour progression by enhancing immune cell suppression. Hyper-sialylation of glycans promotes immune evasion in cancer, but the role of sialyation in stromal cell-mediated immunosuppression is unknown. Here we study changes in sialyltransferase (ST) enzymes and associated surface expressed sialic acid in stromal cells following inflammatory and tumour secretome conditioning. We show that tumour conditioned stromal cells have increased levels of sialyltransferases, α2,3/6 linked sialic acid and siglec ligands. In tumour models of solid (colorectal cancer) and haematological (multiple myeloma) stromal rich tumours, stromal cell sialylation is associated with enhanced immunosuppression. Using datasets and patient samples, we confirm that targeting sialylation in tumour stromal cells reverses immune cell exhaustion. Targeting stromal cell sialylation may represent a novel immune checkpoint to reactivate anti-tumour immunity.

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Loss of PGRMC1 Delays the Progression of Hepatocellular Carcinoma via Suppression of Pro-Inflammatory Immune Responses

Cancers ◽

10.3390/cancers13102438 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2438

Author(s):

Sang R. Lee ◽

Jong Geol Lee ◽

Jun H. Heo ◽

Seong Lae Jo ◽

Jihoon Ryu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Responses ◽

Protein Complexes ◽

Growth Factor Receptor ◽

Nuclear Factor Κb ◽

Survival Duration ◽

Compensatory Proliferation ◽

Epidermal Growth ◽

Hepatocyte Death

Pgrmc1 is a non-canonical progesterone receptor related to the lethality of various types of cancer. PGRMC1 has been reported to exist in co-precipitated protein complexes with epidermal growth factor receptor (EGFR), which is considered a useful therapeutic target in hepatocellular carcinoma (HCC). Here, we investigated whether Pgrmc1 is involved in HCC progression. In clinical datasets, PGRMC1 transcription level was positively correlated with EGFR levels; importantly, PGRMC1 level was inversely correlated with the survival duration of HCC patients. In a diethylnitrosamine (DEN)-induced murine model of HCC, the global ablation of Pgrmc1 suppressed the development of HCC and prolonged the survival of HCC-bearing mice. We further found that increases in hepatocyte death and suppression of compensatory proliferation in the livers of DEN-injured Pgrmc1-null mice were concomitant with decreases in nuclear factor κB (NF-κB)-dependent production of interleukin-6 (IL-6). Indeed, silencing of Pgrmc1 in murine macrophages led to reductions in NF-κB activity and IL-6 production. We found that the anti-proinflammatory effect of Pgrmc1 loss was mediated by reductions in EGFR level and its effect was not observed after exposure of the EGFR inhibitor erlotinib. This study reveals a novel cooperative role of Pgrmc1 in supporting the EGFR-mediated development of hepatocellular carcinoma, implying that pharmacological suppression of Pgrmc1 may be a useful strategy in HCC treatment.

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The emerging role of CXC chemokines in epithelial ovarian cancer

Reproduction ◽

10.1530/rep-12-0153 ◽

2012 ◽

Vol 144 (3) ◽

pp. 303-317 ◽

Cited By ~ 23

Author(s):

Adam Rainczuk ◽

Jyothsna Rao ◽

Jessica Gathercole ◽

Andrew N Stephens

Keyword(s):

Ovarian Cancer ◽

Survival Rate ◽

Immune Responses ◽

Epithelial Ovarian Cancer ◽

Chronic Inflammation ◽

Inflammatory Process ◽

Tumour Progression ◽

Normal Ovary ◽

Specific Symptoms

In recent years, chemokines have generated intense investigations due to their involvement in both physiological and pathological processes of inflammation, particularly in ovarian biology. The physiological process of ovulation in the normal ovary involves various chemokines that mediate the healing of the ruptured endometrium. It is now being reported that many of these chemokines are also associated with the cancer of the ovary. Chronic inflammation underlies the progression of ovarian cancer; therefore, it raises the possibility that chemokines are involved in the inflammatory process and mediate immune responses that may favour or inhibit tumour progression. Ovarian cancer is a gynaecological cancer responsible for highest rate of mortality in women. Although there have been several investigations and advances in surgery and chemotherapy, the survival rate for this disease remains low. This is mainly because of a lack of specific symptoms and biomarkers for detection. In this review, we have discussed the emerging role of the CXC chemokines in epithelial ovarian cancer (EOC). The CXC group of chemokines is gaining importance in the field of ovarian cancer for being angiostatic and angiogenic in function. While there have been several studies on the angiogenesis function, emerging research shows that ELR−CXC chemokines, CXCL9 and CXCL10, are angiostatic. Importantly, the angiostatic chemokines can inhibit the progression of EOC. Given that there are currently no biomarkers or specific therapeutic targets for the disease, these chemokines are emerging as promising targets for therapy.

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