The RANKL inhibitor denosumab in combination with dual checkpoint inhibition is associated with increased CXCL-13 serum concentrations

Schaper-Gerhardt, Katrin; Gutzmer, Ralf; Angela, Yenny; Zimmer, Lisa; Livingstone, Elisabeth; Schadendorf, Dirk; Hassel, Jessica C.; Weishaupt, Carsten; Remes, Bernhard; Kubat, Linda; Spassova, Ivelina; Becker, Jürgen C.

doi:10.1016/j.ejca.2024.113984

European Journal of Cancer

2024

DOI: 10.1016/j.ejca.2024.113984

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The RANKL inhibitor denosumab in combination with dual checkpoint inhibition is associated with increased CXCL-13 serum concentrations

Katrin Schaper-Gerhardt,

Ralf Gutzmer,

Yenny Angela

et al.

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Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Xie,

Li,

et al. 2024

World J Clin Oncol

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Gastric signet-ring cell carcinoma (GSRCC) is a subtype of gastric cancer with distinct phenotype and high risk of peritoneal metastasis. Studies have shown that early GSRCC has a good prognosis, while advanced GSRCC is insensitive to radiotherapy, chemotherapy or immune checkpoint blockade therapy. With technological advancement of single-cell RNA sequencing analysis and cytometry by time of flight mass cytometry, more detailed atlas of tumor microenvironment (TME) in GSRCC and its association with prognosis could be investigated extensively. Recently, two single-cell RNA sequencing studies revealed that GSRCC harbored a unique TME, manifested as highly immunosuppressive, leading to high immune escape. The TME of advanced GSRCC was enriched for immunosuppressive factors, including the loss of CXCL13 +-cluster of differentiation 8+-Tex cells and declined clonal crosstalk among populations of T and B cells. In addition, GSRCC was mainly infiltrated by follicular B cells. The increased proportion of SRCC was accompanied by a decrease in mucosa-associated lymphoid tissue-derived B cells and a significant increase in follicular B cells, which may be one of the reasons for the poor prognosis of GSRCC. By understanding the relationship between immunosuppressive TME and poor prognosis in GSRCC and the underlying mechanism, more effective immunotherapy strategies and improved treatment outcomes of GSRCC can be anticipated.

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Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Xie,

Li,

et al. 2024

World J Clin Oncol

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The RANKL inhibitor denosumab in combination with dual checkpoint inhibition is associated with increased CXCL-13 serum concentrations

Cited by 1 publication

References 31 publications

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

Immunosuppressive tumor microenvironment in gastric signet-ring cell carcinoma

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