bims-trytim 2024-04-28 papers

bims-trytim

Biomed News

on Tryptophan metabolism in tumour-immune microenvironment

Issue of 2024–04–28
nine papers selected by
Jialin Feng, University of Dundee

SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma.
Ferroptosis is an effective strategy for cancer therapy.
Pan-cancer analysis of SLC2A family genes as prognostic biomarkers and therapeutic targets.
SLC27A2 is a potential immune biomarker for hematological tumors and significantly regulates the cell cycle progression of diffuse large B-cell lymphoma.
Identification of the ferroptosis-related prognostic gene signature in mesothelioma.
The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.
Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis.
Regulatory role of CD39 and CD73 in tumor immunity.
The Tumor Microenvironment: Signal Transduction.

Front Immunol. 2024 ;15 1372215

SLC7A11 inhibits ferroptosis and downregulates PD-L1 levels in lung adenocarcinoma.

Zhenyao Huang, Xia Chen, Yun Wang, Jiali Yuan, Jing Li, Wenlu Hang, Hao Meng.

   Introduction: Lung adenocarcinoma (LUAD) is a prevalent form of lung cancer originating from lung glandular cells with low survival rates despite recent therapeutic advances due to its diverse and complex nature. Recent evidence suggests a link between ferroptosis and the effectiveness of anti-PD-L1 therapy, with potential synergistic effects.
Methods: Our study comprehensively analyzed the expression patterns of ferroptosis regulators in LUAD and their association with prognosis and PD-L1 expression. Furthermore, we identified two distinct subtypes of LUAD through consensus clustering of ferroptosis regulators, revealing significant tumor heterogeneity, divergent PD-L1 expression, and varying prognoses between the subtypes.
Results: Among the selected ferroptosis regulators, SLC7A11 emerged as an independent prognostic marker for LUAD patients and exhibited a negative correlation with PD-L1 expression. Subsequent investigations revealed high expression of SLC7A11 in the LUAD population. In vitro experiments demonstrated that overexpression of SLC7A11 led to reduced PD-L1 expression and inhibited ferroptosis in A549 cells, underscoring the significant role of SLC7A11 in LUAD. Additionally, pan-cancer analyses indicated an association between SLC7A11 and the expression of immune checkpoint genes across multiple cancer types with poor prognoses.
Discussion: From a clinical standpoint, these findings offer a foundation for identifying and optimizing potential combination strategies to enhance the therapeutic effectiveness of immune checkpoint inhibitors and improve the prognosis of patients with LUAD.

Keywords:  LUAD; PD-L1; SLC7A11; ferroptosis; immune cell infiltration

DOI:  https://doi.org/10.3389/fimmu.2024.1372215
Med Oncol. 2024 Apr 23. 41(5): 124

Ferroptosis is an effective strategy for cancer therapy.

Afrasyab Khan, Yu Huo, Yilei Guo, Juanjuan Shi, Yongzhong Hou.

  Ferroptosis is a form of intracellular iron-dependent cell death that differs from necrosis, autophagy and apoptosis. Intracellular iron mediates Fenton reaction resulting in lipid peroxidation production, which in turn promotes cell death. Although cancer cell exhibit's ability to escape ferroptosis by multiple pathways such as SLC7A11, GPX4, induction of ferroptosis could inhibit cancer cell proliferation, migration and invasion. In tumor microenvironment, ferroptosis could affect immune cell (T cells, macrophages etc.) activity, which in turn regulates tumor immune escape. In addition, ferroptosis in cancer cells could activate immune cell activity by antigen processing and presentation. Therefore, ferroptosis could be an effective strategy for cancer therapy such as chemotherapy, radiotherapy, and immunotherapy. In this paper, we reviewed the role of ferroptosis on tumor progression and therapy, which may provide a strategy for cancer treatment.

Keywords:  Ferroptosis; Therapy; Tumor immune evasion; Tumor microenvironment

DOI:  https://doi.org/10.1007/s12032-024-02317-5
Heliyon. 2024 Apr 30. 10(8): e29655

Pan-cancer analysis of SLC2A family genes as prognostic biomarkers and therapeutic targets.

Yating Liu, Xinyu Li, Jie Yang, Shanshan Chen, Changyu Zhu, Yijun Shi, Shoutao Dang, Weitao Zhang, Wei Li.

   Background: The major facilitator superfamily glucose transporters (GLUTs), encoded by solute carrier 2A (SLC2A) genes, mediate the transmembrane movement and uptake of glucose. To satisfy the improved energy demands, glycolysis flux is increased in cancers compared with healthy tissues. Multiple diseases, including cancer, have been associated with GLUTs. Nevertheless, not much research has been done on the functions of SLC2As in pan-cancer prognosis or their clinical treatment potential.
Methods: The SLC2A family genes' level of expression and prognostic values were analyzed in relation to pan-cancer. We then examined the association among SLC2As expression and TME, Stemness score, clinical characteristics, immune subtypes, and drug sensitivity. We merged bioinformatics analysis techniques with up-to-date public databases. Additionally, SLC2As from the KOBAS database were subjected to enrichment analysis.
Results: We discovered that SLC2As' gene expression differed significantly between normal tissues and many malignancies. A number of tumors from various databases demonstrate a relationship between prognosis and SLC2A family gene expression. For instance, SLC2A2 and SLC2A5 were associated with the overall survival (OS) of hepatocellular carcinoma. SLC2A1 was associated with the OS of lung adenocarcinoma and pancreatic adenocarcinoma. Moreover, the SLC2A family gene expression is significantly correlated with the pan-cancer stromal and immune scores, and the RNA and DNA stemness scores. Furthermore, we found that the majority of SLC2As had a strong correlation with the tumor stages in KIRC. The immunological subtypes and all members of the SLC2A gene family exhibited a substantial correlation. Moreover, pathways containing insulin resistance and adipocytokine signaling pathway may influence the progression of some cancers. Finally, there is a significant positive or negative connection between drug sensitivity and SLC2A1 expression.
Conclusion: Our research highlights the significant promise of SLC2As as prognostic indicators and offers insightful approaches for upcoming exploration of SLC2As as putative therapeutic targets in malignancies.

Keywords:  Pan-cancer; Prognosis; SLC2A family genes; Therapeutic targets; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.heliyon.2024.e29655
BMC Med Genomics. 2024 Apr 25. 17(1): 105

SLC27A2 is a potential immune biomarker for hematological tumors and significantly regulates the cell cycle progression of diffuse large B-cell lymphoma.

Yi Wang, Xue Chen, Yun Li, Zhixue Zhang, Leiming Xia, Jiang Jiang, Yuqin Chai, Ziming Wang, Yu Wan, Tongyu Li, Fengbo Jin, Hongxia Li.

   BACKGROUND: Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported.
METHOD: This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors.
RESULT: This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells.
CONCLUSION: In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

Keywords:  Apoptosis; Cell cycle; DLBCL; Fatty acid metabolism; SLC27A2

DOI:  https://doi.org/10.1186/s12920-024-01853-3
Gene. 2024 Apr 24. pii: S0378-1119(24)00379-2. [Epub ahead of print] 148498

Identification of the ferroptosis-related prognostic gene signature in mesothelioma.

Zairui Wang, Jialin Huang, MinYang, Liren Fu, Shijie Liu, Jianghua Huang, Jingjing Han, Xiaohui Zhao.

  Mesothelioma, an uncommon yet highly aggressive malignant neoplasm, presents challenges in the effectiveness of current therapeutic approaches. Ferroptosis, a non-apoptotic mechanism of cellular demise, exhibits a substantial association with the progression of diverse cancer forms. It is important to acknowledge that there exists a significant association between ferroptosis and the advancement of various forms of cancer. Nevertheless, the precise role of ferroptosis regulatory factors within the context of mesothelioma remains enigmatic. In our investigation, we initially scrutinized the prognostic significance of 24 ferroptosis regulatory factors in the realm of mesothelioma. Our observations unveiled that heightened expression levels of CARS1, CDKN1A, TFRC, FANCD2, FDFT1, HSPB1, SLC1A5, SLC7A11, coupled with reduced DPP4 expression, were indicative of an unfavorable prognosis. Built upon the nine previously discussed prognostic genes, the ferroptosis prognostic model offers a reliable means to forecast mesothelioma patients' survival with a substantial degree of precision. Furthermore, a notable correlation emerged between these prognostic ferroptosis regulators and parameters such as immune cell infiltration, tumor mutation burden, microsatellite instability, and PD-L1 expression in the context of mesothelioma. Within this cadre of nine ferroptosis regulatory factors with prognostic relevance, FANCD2 exhibited the most pronounced prognostic influence, as elucidated by our analyses. Subsequently, we executed a validation process employing clinical specimens sourced from our institution, thus confirming that heightened FANCD2 expression is a discernible harbinger of an adverse prognosis in the context of mesothelioma. In vitro experiments revealed that knocking down FANCD2 markedly suppressed the proliferation, migration, and ability of mesothelioma cells to attract immune cells. Furthermore, our findings also showed that reducing FANCD2 levels heightened the vulnerability of mesothelioma cells to inducers of ferroptosis. Furthermore, an extensive pan-cancer analysis uncovered a robust association between FANCD2 and the gene expression linked to immune checkpoints, thereby signifying an adverse prognosis across a broad spectrum of cancer types. Additional research is warranted to validate these findings.

Keywords:  FANCD2; Ferroptosis; Immune Infiltration; Mesothelioma

DOI:  https://doi.org/10.1016/j.gene.2024.148498
Front Oncol. 2024 ;14 1363695

The role of alpha-fetoprotein in the tumor microenvironment of hepatocellular carcinoma.

Yan Lu, Bo Lin, Mengsen Li.

  Hepatocellular carcinoma (HCC) is a prevalent malignant cancer worldwide, characterized by high morbidity and mortality rates. Alpha-fetoprotein (AFP) is a glycoprotein synthesized by the liver and yolk sac during fetal development. However, the serum levels of AFP exhibit a significant correlation with the onset and progression of HCC in adults. Extensive research has demonstrated that the tumor microenvironment (TME) plays a crucial role in the malignant transformation of HCC, and AFP is a key factor in the TME, promoting HCC development. The objective of this review was to analyze the existing knowledge regarding the role of AFP in the TME. Specifically, this review focused on the effect of AFP on various cells in the TME, tumor immune evasion, and clinical application of AFP in the diagnosis and treatment of HCC. These findings offer valuable insights into the clinical treatment of HCC.

Keywords:  AFP; hepatocellular carcinoma; immune escape; immunotherapy; liver cancer stem cells; tumor microenvironment

DOI:  https://doi.org/10.3389/fonc.2024.1363695
Cell Death Discov. 2024 Apr 22. 10(1): 189

Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis.

Cong Chen, Jian Liu, Xia Lin, Aizhai Xiang, Qianwei Ye, Jufeng Guo, Tao Rui, Jian Xu, Shufang Hu.

Cancer-associated fibroblasts (CAFs), the main stromal component of the tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms of regulated cell death (RCD) in adjacent tumor cells, thus involving cancer proliferation, therapy resistance, and immune exclusion. Here, we present a brief introduction to CAFs and basic knowledge of RCD, including apoptosis, autophagy, ferroptosis, and pyroptosis. In addition, we further summarize the different types of RCD in tumors that are mediated by CAFs, as well as the effects of these modes of RCD on CAFs. This review will deepen our understanding of the interactions between CAFs and RCD and might offer novel therapeutic avenues for future cancer treatments.

DOI: https://doi.org/10.1038/s41420-024-01958-9
Future Oncol. 2024 Apr 23.

Regulatory role of CD39 and CD73 in tumor immunity.

Nicole Kaplinsky, Kada Williams, Dean Watkins, Molly Adams, Laura Stanbery, John Nemunaitis.

  CD39 is the rate-limiting enzyme for the molecular signal cascade leading to the generation of ADP and adenosine monophosphate (AMP). In conjunction with CD73, CD39 converts adenosine triphosphate (ATP) to ADP and AMP, which leads to the accumulation of immunosuppressive adenosine in the tumor microenvironment. This review focuses on the role of CD39 and CD73 in immune response and malignant progression, including the expression of CD39 within the tumor microenvironment and its relationship to immune effector cells, and its role in antigen presentation. The role of CD39- and CD73-targeting therapeutics and cancer-directed clinical trials investigating CD39 modulation are also explored.

Keywords:  CD39; CD73; ENTPD1; adenosine pathway; antigen; immunotherapy; tumor microenvironment

DOI:  https://doi.org/10.2217/fon-2023-0871
Biomolecules. 2024 Apr 04. pii: 438. [Epub ahead of print]14(4):

The Tumor Microenvironment: Signal Transduction.

Xianhong Zhang, Haijun Ma, Yue Gao, Yabing Liang, Yitian Du, Shuailin Hao, Ting Ni.

  In the challenging tumor microenvironment (TME), tumors coexist with diverse stromal cell types. During tumor progression and metastasis, a reciprocal interaction occurs between cancer cells and their environment. These interactions involve ongoing and evolving paracrine and proximal signaling. Intrinsic signal transduction in tumors drives processes such as malignant transformation, epithelial-mesenchymal transition, immune evasion, and tumor cell metastasis. In addition, cancer cells embedded in the tumor microenvironment undergo metabolic reprogramming. Their metabolites, serving as signaling molecules, engage in metabolic communication with diverse matrix components. These metabolites act as direct regulators of carcinogenic pathways, thereby activating signaling cascades that contribute to cancer progression. Hence, gaining insights into the intrinsic signal transduction of tumors and the signaling communication between tumor cells and various matrix components within the tumor microenvironment may reveal novel therapeutic targets. In this review, we initially examine the development of the tumor microenvironment. Subsequently, we delineate the oncogenic signaling pathways within tumor cells and elucidate the reciprocal communication between these pathways and the tumor microenvironment. Finally, we give an overview of the effect of signal transduction within the tumor microenvironment on tumor metabolism and tumor immunity.

Keywords:  signaling pathways; tumor immunity; tumor metabolism; tumor microenvironment

DOI:  https://doi.org/10.3390/biom14040438