bims-trytim 2024-05-12 papers

Issue of 2024–05–12
three papers selected by
Jialin Feng, University of Dundee

J Hematol Oncol. 2024 May 08. 17(1): 31

Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.

Hao Lin, Chaxian Liu, Ankang Hu, Duanwu Zhang, Hui Yang, Ying Mao.

Glioblastoma (GBM), the predominant and primary malignant intracranial tumor, poses a formidable challenge due to its immunosuppressive microenvironment, thereby confounding conventional therapeutic interventions. Despite the established treatment regimen comprising surgical intervention, radiotherapy, temozolomide administration, and the exploration of emerging modalities such as immunotherapy and integration of medicine and engineering technology therapy, the efficacy of these approaches remains constrained, resulting in suboptimal prognostic outcomes. In recent years, intensive scrutiny of the inhibitory and immunosuppressive milieu within GBM has underscored the significance of cellular constituents of the GBM microenvironment and their interactions with malignant cells and neurons. Novel immune and targeted therapy strategies have emerged, offering promising avenues for advancing GBM treatment. One pivotal mechanism orchestrating immunosuppression in GBM involves the aggregation of myeloid-derived suppressor cells (MDSCs), glioma-associated macrophage/microglia (GAM), and regulatory T cells (Tregs). Among these, MDSCs, though constituting a minority (4-8%) of CD45+ cells in GBM, play a central component in fostering immune evasion and propelling tumor progression, angiogenesis, invasion, and metastasis. MDSCs deploy intricate immunosuppressive mechanisms that adapt to the dynamic tumor microenvironment (TME). Understanding the interplay between GBM and MDSCs provides a compelling basis for therapeutic interventions. This review seeks to elucidate the immune regulatory mechanisms inherent in the GBM microenvironment, explore existing therapeutic targets, and consolidate recent insights into MDSC induction and their contribution to GBM immunosuppression. Additionally, the review comprehensively surveys ongoing clinical trials and potential treatment strategies, envisioning a future where targeting MDSCs could reshape the immune landscape of GBM. Through the synergistic integration of immunotherapy with other therapeutic modalities, this approach can establish a multidisciplinary, multi-target paradigm, ultimately improving the prognosis and quality of life in patients with GBM.

DOI: https://doi.org/10.1186/s13045-024-01544-7

Eur J Cell Biol. 2024 May 08. pii: S0171-9335(24)00035-9. [Epub ahead of print]103(2): 151418

Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders.

Takeshi Kondo, Yuka Okada, Saika Shizuya, Naoko Yamaguchi, Shigetsugu Hatakeyama, Kenta Maruyama.

The nervous and immune systems are highly developed, and each performs specialized physiological functions. However, they work together, and their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, and more general metabolites, are essential for the appropriate regulation of both systems. Tryptophan, an essential amino acid, is converted into functional molecules such as serotonin and kynurenine, both of which play important roles in the nervous and immune systems. The role of kynurenine metabolites in neurodegenerative and psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity of the kynurenine pathway is a critical risk factor for septic shock. In this review, we first outline neuroimmune interactions and tryptophan derivatives and then summarized the changes in tryptophan metabolism in neurological disorders. Finally, we discuss the potential of tryptophan derivatives as therapeutic targets for neuroimmune disorders.

Keywords: Kynurenine; Neuroimmunology; Psychiatric disorders; Sepsis; Serotonin; Tryptophan

DOI: https://doi.org/10.1016/j.ejcb.2024.151418

Mol Metab. 2024 May 03. pii: S2212-8778(24)00083-8. [Epub ahead of print] 101952

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.

Kiavash Hushmandi, Behzad Einollahi, Seyed Hassan Saadat, E Hui Clarissa Lee, Marzieh Ramezani Farani, Elena Okina, Yun Suk Huh, Noushin Nabavi, Shokooh Salimimoghadam, Alan Prem Kumar.

Solute carrier (SLC), a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment. Amino acids are fundamental building blocks of cells, playing essential roles not only in protein synthesis but also in nutrient sensing, and in signaling pathways that can promote tumorigenesis. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. Amino acid uptake by SLCs positively affects tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although a body of studies evaluated the function of SLC7A11 and SLC1A5, some of the SLC proteins are not studied sufficiently in cancer. In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids, as one of the most important materials that cancer cells need, and their transporters within the SLC superfamily.

Keywords: Amino acid; Cancer; Cancer metabolism; Nutrient sensing; SLC

DOI: https://doi.org/10.1016/j.molmet.2024.101952