Pan‐cancer analysis identifies <scp><i>CD300</i></scp> molecules as potential immune regulators and promising therapeutic targets in acute myeloid leukemia

Xu, Zi‐jun; Jin, Yue; Zhang, Xin‐long; Xia, Pei‐hui; Wen, Xiang‐mei; Ma, Ji‐chun; Jiang, Lin; Qian, Jun

doi:10.1002/cam4.4905

Cited by 7 publications

(2 citation statements)

References 69 publications

(179 reference statements)

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“…Both receptors are expressed by virtually all leukocytes and possibly recognize lipids that are exposed on the outer leaflet of the plasma membrane of dead and activated cell. CD300 receptors are also highly expressed by human cancer cells, especially in acute myeloid leukemia ( 193 ). To date, their therapeutic potential in cancer immunotherapy remains to be elucidated.…”

Section: Irs Expressed By Pdcs and Their Role In Physiology And Tumorsmentioning

confidence: 99%

Inhibitory receptors of plasmacytoid dendritic cells as possible targets for checkpoint blockade in cancer

Tiberio,

Laffranchi,

Zucchi

et al. 2024

Front. Immunol.

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Plasmacytoid dendritic cells (pDCs) are the major producers of type I interferons (IFNs), which are essential to mount antiviral and antitumoral immune responses. To avoid exaggerated levels of type I IFNs, which pave the way to immune dysregulation and autoimmunity, pDC activation is strictly regulated by a variety of inhibitory receptors (IRs). In tumors, pDCs display an exhausted phenotype and correlate with an unfavorable prognosis, which largely depends on the accumulation of immunosuppressive cytokines and oncometabolites. This review explores the hypothesis that tumor microenvironment may reduce the release of type I IFNs also by a more pDC-specific mechanism, namely the engagement of IRs. Literature shows that many cancer types express de novo, or overexpress, IR ligands (such as BST2, PCNA, CAECAM-1 and modified surface carbohydrates) which often represent a strong predictor of poor outcome and metastasis. In line with this, tumor cells expressing ligands engaging IRs such as BDCA-2, ILT7, TIM3 and CD44 block pDC activation, while this blocking is prevented when IR engagement or signaling is inhibited. Based on this evidence, we propose that the regulation of IFN secretion by IRs may be regarded as an “innate checkpoint”, reminiscent of the function of “classical” adaptive immune checkpoints, like PD1 expressed in CD8+ T cells, which restrain autoimmunity and immunopathology but favor chronic infections and tumors. However, we also point out that further work is needed to fully unravel the biology of tumor-associated pDCs, the neat contribution of pDC exhaustion in tumor growth following the engagement of IRs, especially those expressed also by other leukocytes, and their therapeutic potential as targets of combined immune checkpoint blockade in cancer immunotherapy.

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Section: Irs Expressed By Pdcs and Their Role In Physiology And Tumorsmentioning

confidence: 99%

Inhibitory receptors of plasmacytoid dendritic cells as possible targets for checkpoint blockade in cancer

Tiberio,

Laffranchi,

Zucchi

et al. 2024

Front. Immunol.

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“…Then we performed meta-analyses to combine p values and hazard ratios (HRs) using the survcomp package. The LSC17 and LI24 prognostic models were constructed as previously described 16,17 .…”

Section: Survival Analysismentioning

confidence: 99%

Comprehensive characterization of TGFB1 across hematological malignancies

Wang,

Zhang,

Zhang

et al. 2023

Sci Rep

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TGFB1, which encodes TGF-β1, a potent cytokine regulating varies cellular processes including immune responses. TGF-β1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.

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Pan‐cancer analysis identifies CD300 molecules as potential immune regulators and promising therapeutic targets in acute myeloid leukemia

Jin

Zhang

et al. 2022

Cancer Medicine

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Background CD300s are a group of proteins playing vital roles in immune responses. However, much is yet to be elucidated regarding the expression patterns and clinical significances of CD300s in cancers. Methods In this study, we comprehensively investigated CD300s in a pan‐cancer manner using multi‐omic data from The Cancer Genome Atlas. We also studied the relationship between CD300s and the immune landscape of AML. Results We found that CD300A ‐ CD300LF were generally overexpressed in tumors (especially AML), whereas CD300LG was more often downregulated. In AML, transactivation of CD300A was not mediated by genetic alterations but by histone modification. Survival analyses revealed that high CD300A ‐ CD300LF expression predicted poor outcome in AML patients; the prognostic value of CD300A was validated in seven independent datasets and a meta dataset including 1115 AML patients. Furthermore, we demonstrated that CD300A expression could add prognostic value in refining existing risk models in AML. Importantly, CD300A ‐ CD300LF expression was closely associated with T‐cell dysfunction score and could predict response to AML immunotherapy. Also, CD300A was found to be positively associated with HLA genes and critical immune checkpoints in AML, such as VISTA , CD86 , CD200R1 , Tim‐3 , and the LILRB family genes. Conclusions Our study demonstrated CD300s as potential prognostic biomarker and an ideal immunotherapy target in AML, which warrants future functional and clinical studies.

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Pan‐cancer analysis identifies CD300 molecules as potential immune regulators and promising therapeutic targets in acute myeloid leukemia

Cited by 7 publications

References 69 publications

Inhibitory receptors of plasmacytoid dendritic cells as possible targets for checkpoint blockade in cancer

Inhibitory receptors of plasmacytoid dendritic cells as possible targets for checkpoint blockade in cancer

Comprehensive characterization of TGFB1 across hematological malignancies

Pan‐cancer analysis identifies CD300 molecules as potential immune regulators and promising therapeutic targets in acute myeloid leukemia

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