Immune Checkpoint LAG3 and Its Ligand FGL1 in Cancer

Shi, An‐Ping; Tang, Xiyang; Xiong, Yanlu; Zheng, Kaifu; Liu, Yujian; Shi, Xian-Gui; Lv, Yao; Jiang, Tao; Ma, Nan; Zhao, Jinbo

doi:10.3389/fimmu.2021.785091

Cited by 94 publications

(94 citation statements)

References 99 publications

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“…Further studies reproduced the anti-tumor effect of TIGIT using human PBMCs [96,97]. These findings of efficacy of targeting other co-inhibitory molecules led to clinical trials of LAG-3 [98], TIM-3 [99], and TIGIT [100] in patients with cancer. In summary, many studies and trials have been conducted using ICIs to treat cancer.…”

Section: Characteristicsmentioning

confidence: 81%

Dendritic Cell-Based Immunotherapy in Hot and Cold Tumors

Kang

Lee

2022

IJMS

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Dendritic cells mediate innate and adaptive immune responses and are directly involved in the activation of cytotoxic T lymphocytes that kill tumor cells. Dendritic cell-based cancer immunotherapy has clinical benefits. Dendritic cell subsets are diverse, and tumors can be hot or cold, depending on their immunogenicity; this heterogeneity affects the success of dendritic cell-based immunotherapy. Here, we review the ontogeny of dendritic cells and dendritic cell subsets. We also review the characteristics of hot and cold tumors and briefly introduce therapeutic trials related to hot and cold tumors. Lastly, we discuss dendritic cell-based cancer immunotherapy in hot and cold tumors.

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Section: Characteristicsmentioning

confidence: 81%

Dendritic Cell-Based Immunotherapy in Hot and Cold Tumors

Kang

Lee

2022

IJMS

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“…However, it was reported that LAG3 expression was associated with an improved overall survival (OS) compared to patients without LAG3 expression in oesophageal adenocarcinoma ( 27 ). LAG3 may serve as a biomarker for a strong immune response, and the two opposite immune functions (positively or negatively) of LAG3 can be attributed to the complexity of tumor immune microenvironment and tumor heterogeneity ( 28 ). The function of LAG3 in melanoma needs further experiments to verify.…”

Section: Resultsmentioning

confidence: 99%

Exploring Tumor Immune Microenvironment and Its Associations With Molecular Characteristics in Melanoma

et al. 2022

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BackgroundThe tumor microenvironment (TME), which involves infiltration of multiple immune cells into the tumor tissues, plays an essential role in clinical benefit to therapy. The chemokines and their receptors influence migration and functions of both tumor and immune cells. Also, molecular characteristics are associated with the efficacy of melanoma therapy. However, there lacked exploration of immune characteristics and the association with molecular characteristics.MethodsWe collected the currently available 569 melanoma samples that had both the genomic and transcriptional data from TCGA and SRA databases. We first identified TME subtypes based on the developed immune signatures, and then divided the samples into two immune cohorts based on the immune score. Next, we estimated the compositions of the immune cells of the two cohorts, and performed differential expression genes (DEGs) and functional enrichments. In addition, we investigated the interactions of chemokines and their receptors under immune cells. Finally, we explored the genomic characteristics under different immune subtypes.ResultsTME type D had a better prognosis among the four subtypes. The high-immunity cohort had significantly high 16 immune cells. The 63 upregulated and 384 downregulated genes in the high-immunity cohort were enriched in immune-related biological processes, and keratin, pigmentation and epithelial cells, respectively. The correlations of chemokines and their receptors with immune cell infiltration, such as CCR5-CCL4/CCL5 and CXCR3-CXCL9/CXCL10/CXCL11/CXCL13 axis, showed that the recruitments of 11 immune cells, such as CD4T cells and CD8T cells, were modulated by chemokines and their receptors. The proportions of the four TME subtypes in each molecular subtype were comparable. The two driver genes, CDKN2A and PRB2, had significantly different MAFs between the high-immunity and low-immunity.ConclusionWe dissected the characteristics of immune infiltration, the interactions of chemokines and their receptors under immune cells, and the correlation of molecular and immune characteristics. Our work will enable the reasonable selection of anti-melanoma treatments and accelerate the development of new therapeutic strategies for melanoma.

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“…This contradictory pattern has also been observed in breast cancer. In ER - and ER + breast cancer, high expression of LAG-3 predicted a favorable outcome ( 109 , 110 ). However, dual-positive LAG-3 and PD-1 were correlated with an unfavorable prognosis in terms of decreased DFS ( 111 ).…”

Section: Preclinical Data In Esophageal Cancermentioning

confidence: 99%

Novel Immune Checkpoints in Esophageal Cancer: From Biomarkers to Therapeutic Targets

et al. 2022

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Esophageal cancer ranks as the sixth most common cause of cancer death worldwide. Due to the limited efficacy of conventional therapeutic strategies, including surgery, chemotherapy, and radiotherapy, treatments are still far from satisfactory in terms of survival, prompting the search for novel treatment methods. Immune checkpoints play crucial roles in immune evasion mediated by tumor cells, and successful clinical outcomes have been achieved via blocking these pathways. However, only a small fraction of patients can benefit from current immune checkpoint inhibitors targeting programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated protein-4. Unfortunately, some patients show primary and/or acquired resistance to immune checkpoint inhibitors. Until now, novel immune checkpoint pathways have rarely been studied in esophageal cancer, and there is a great need for biomarkers to predict who will benefit from existing strategies. Herein, we primarily discuss the roles of new immune checkpoints as predictive biomarkers and therapeutic targets for esophageal cancer. In addition, we summarize the ongoing clinical trials and provide future research directions targeting these pathways.

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Immune Checkpoint LAG3 and Its Ligand FGL1 in Cancer

Cited by 94 publications

References 99 publications

Dendritic Cell-Based Immunotherapy in Hot and Cold Tumors

Dendritic Cell-Based Immunotherapy in Hot and Cold Tumors

Exploring Tumor Immune Microenvironment and Its Associations With Molecular Characteristics in Melanoma

Novel Immune Checkpoints in Esophageal Cancer: From Biomarkers to Therapeutic Targets

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