Expression of immune checkpoint molecules programmed death protein 1, programmed death‐ligand 1 and inducible T‐cell co‐stimulator in mycosis fungoides and Sézary syndrome: association with disease stage and clinical outcome*

Raimondo, Cosimo Di; Rubio-Gonzalez, Belen; Palmer, Joycelynne; Weisenburger, Dennis D.; Zain, Jasmine; Wu, Xiwei; Han, Zhen; Rosen, Steven T.; Song, Joo Y.; Querfeld, Christiane

doi:10.1111/bjd.21063

Cited by 12 publications

(9 citation statements)

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“…For example, gastric cancer patients with abundant ICOS+Foxp3+ TILs had advanced stages and shorter recurrence-free survival, 25 and high expression of ICOS was associated with an advanced clinical stage and poor OS among patients with cutaneous T-cell lymphoma. 26 In contrast, ICOS enhances the activation of CD4 and CD8 effector T cells to exert an antitumor function in colorectal cancer. 27 28 In this study, we found that high expression of ICOS mRNA, but not the protein level, is a protective factor for OS and EFS in NB patients, but this requires further verification in a larger patient cohort.…”

Section: Discussionmentioning

confidence: 99%

Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

Zeng

et al. 2023

J Immunother Cancer

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BackgroundNeuroblastoma (NB) places a substantial health burden on families worldwide. This study aimed to develop an immune checkpoint-based signature (ICS) based on the expression of immune checkpoints to better assess patient survival risk and potentially guide patient selection for immunotherapy of NB.MethodsImmunohistochemistry integrated with digital pathology was used to determine the expression levels of 9 immune checkpoints in 212 tumor tissues used as the discovery set. The GSE85047 dataset (n=272) was used as a validation set in this study. In the discovery set, the ICS was constructed using a random forest algorithm and confirmed in the validation set to predict overall survival (OS) and event-free survival (EFS). Kaplan-Meier curves with a log-rank test were drawn to compare the survival differences. A receiver operating characteristic (ROC) curve was applied to calculate the area under the curve (AUC).ResultsSeven immune checkpoints, including PD-L1, B7-H3, IDO1, VISTA, T-cell immunoglobulin and mucin domain containing-3 (TIM-3), inducible costimulatory molecule (ICOS) and costimulatory molecule 40 (OX40), were identified as abnormally expressed in NB in the discovery set. OX40, B7-H3, ICOS and TIM-3 were eventually selected for the ICS model in the discovery set, and 89 patients with high risk had an inferior OS (HR 15.91, 95% CI 8.87 to 28.55, p<0.001) and EFS (HR 4.30, 95% CI 2.80 to 6.62, p<0.001). Furthermore, the prognostic value of the ICS was confirmed in the validation set (p<0.001). Multivariate Cox regression analysis demonstrated that age and the ICS were independent risk factors for OS in the discovery set (HR 6.17, 95% CI 1.78 to 21.29 and HR 1.18, 95% CI 1.12 to 1.25, respectively). Furthermore, nomogram A combining the ICS and age demonstrated significantly better prognostic value than age alone in predicting the patients’ 1-year, 3-year and 5-year OS in the discovery set (1 year: AUC, 0.891 (95% CI 0.797 to 0.985) vs 0.675 (95% CI 0.592 to 0.758); 3 years: 0.875 (95% CI 0.817 to 0.933) vs 0.701 (95% CI 0.645 to 0.758); 5 years: 0.898 (95% CI 0.851 to 0.940) vs 0.724 (95% CI 0.673 to 0.775), respectively), which was confirmed in the validation set.ConclusionsWe propose an ICS that significantly differentiates between low-risk and high-risk patients, which might add prognostic value to age and provide clues for immunotherapy in NB.

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Section: Discussionmentioning

confidence: 99%

Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

Zeng

et al. 2023

J Immunother Cancer

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“…Furthermore, the results from nine samples of three patients with patch, plaque and tumour lesions are of particular interest. They were analysed with a seven‐colour multispectral image to ascertain the expression of checkpoint markers in distinct cell populations 1 . The authors found PD‐L1 predominantly expressed on CD163 + macrophages and not on the T lymphocytes, which has also been reported in other types of cutaneous lymphomas 1,2 …”

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confidence: 92%

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confidence: 99%

“…In this issue of the BJD , Di Raimondo and colleagues provide new information about expression of checkpoint molecules in mycosis fungoides and Sézary syndrome. They established a combined checkpoint marker score covering expression of programmed death protein 1 (PD‐1), programmed death ligand 1 (PD‐L1) and inducible T‐cell costimulator (ICOS) and found that a high score was associated with advanced‐stage disease and lower overall survival 1 …”

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confidence: 99%

“…Recent papers show that multistaining is critical to localize coexpression of immune checkpoint molecules and tumour cells or cell types of the tumour microenvironment (TME) 1–3 . Especially in lymphoma, it is difficult to differentiate neoplastic from reactive lymphocytes and from some other cells of the TME, based on morphological criteria alone 1–3 . Even if it seems to be easier in solid tumours, differentiation is also often not possible, because in areas of close interaction of tumour cells and the TME (especially macrophages), the morphologies of the two cell populations can be quite similar 4,5 …”

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Multistaining for a better understanding of lymphoma biology

Mitteldorf

2022

Br J Dermatol

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signalling as a central hub in coordinating inflammatory responses in HS. However, the multitude of pathways affected by its inhibition strongly suggests that, in contrast to other IL-17-driven diseases such as psoriasis, the inflammatory response in HS is much broader, as is increasingly recognized.Even though most translational investigations have focused on IL-17A, significant overproduction of other IL-17 isoforms (e.g. IL-17C and IL-17F) is observed in HS tissue, and this may contribute to disease activity. Interestingly, heteromeric isoforms with IL-17RA can bind both IL-17A and IL-17C, thus reaching further than secukinumab, which targets IL-17A, whereas bimekizumab inhibits IL-17A, IL-17F and IL-17AF.In conclusion, this study by Navrazhina and colleagues offers both mechanistic insights and biomarker candidates to better characterize the molecular response to IL-17RA inhibition. Moreover, their study provides directly applicable strategies to dissect inflammatory patterns in patients with HS as a prerequisite for a precision medicine-driven approach.

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New horizons in the mechanisms and therapeutic strategies for PD-L1 protein degradation in cancer

Li,

Yu,

Yuan

et al. 2024

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Expression of immune checkpoint molecules programmed death protein 1, programmed death‐ligand 1 and inducible T‐cell co‐stimulator in mycosis fungoides and Sézary syndrome: association with disease stage and clinical outcome*

Abstract: Data availabilityOur datasets have been submitted to the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus [(GEO); https://www.

Cited by 12 publications

References 42 publications

Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

Cross-cohort analysis identified an immune checkpoint-based signature to predict the clinical outcomes of neuroblastoma

Multistaining for a better understanding of lymphoma biology

New horizons in the mechanisms and therapeutic strategies for PD-L1 protein degradation in cancer

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