Immunotherapy in Testicular Germ Cell Tumors

Kalavska, Katarína; Schmidtova, Silvia; Chovanec, Michal; Mego, Michal

doi:10.3389/fonc.2020.573977

Cited by 31 publications

(27 citation statements)

References 55 publications

(63 reference statements)

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“…Importantly, it could be an adverse effect of anti-PD1 therapy, emphasizing the role of immune checkpoints in maintaining testicular immune homeostasis [ 37 ]. On the contrary, the lack of adequate immune surveillance may participate in the development of GCTs [ 38 ]. To achieve an effective anti-tumor response, testis probably needs to abnegate its immune privilege, similarly as it is during microbial infections.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, PD-L1 expression on macrophages correlates with an activated immune microenvironment and prolonged survival in hepatocellular carcinoma [ 48 ], and, importantly, in primary testicular lymphoma [ 49 ]. Alternatively, the expression of immune checkpoint proteins may reduce the proinflammatory environment, thus, inhibiting the so-called tumor-promoting inflammation [ 5 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

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Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes

Pęksa

Kunc

Popęda

et al. 2021

Cancers

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In the current study, we aimed to investigate whether expression of immune checkpoint proteins (V-domain Ig suppressor of T cell activation (VISTA) and programmed death-ligand 1 (PD-L1)) and markers of systemic inflammation could predict progression/relapse and death in the cohort of 180 patients with testicular germ-cell tumors (GCTs). Expression of PD-L1 and VISTA was assessed by immunohistochemistry utilizing tissue microarrays. To estimate systemic inflammation neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were calculated. We found high PD-L1 and VISTA expression on tumor-associated immune cells (TAICs) in 89 (49.44%) and 63 (37.22%) of GCTs, respectively, whereas tumor cells besides trophoblastic elements were almost uniformly negative. High PD-L1 was associated with seminomatous histology and lower stage. Relapses in stage I patients occurred predominantly in cases with low numbers of PD-L1 and VISTA-expressing TAICs. In stage II/III disease, the combination of low VISTA-expressing TAICs and high PLR was identified as predictor of shorter event-free survival (HR 4.10; 1.48–11.36, p = 0.006) and overall survival (HR 15.56, 95% CI 1.78–135.51, p = 0.001) independently of tumor histology and location of metastases. We demonstrated that the assessment of immune checkpoint proteins on TAICs may serve as a valuable prognostic factor in patients with high-risk testicular GCTs. Further study is warranted to explore the predictive utility of these biomarkers in GCTs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes

Pęksa

Kunc

Popęda

et al. 2021

Cancers

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“…Low response rates have been attributed to the immunosuppressive microenvironment of testicular tissue. TGCTs have been observed to have a low tumor mutational burden and have varying expression of PD-1/PD-L1 [145,146].…”

Section: Testicular Cancermentioning

confidence: 99%

Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

Labadie

Balar

Luke

2021

Cancers

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Cancers of the genitourinary (GU) tract are common malignancies in both men and women and are a major source of morbidity and mortality. Immune checkpoint inhibitors (ICI) targeting CTLA-4, PD-1 or PD-L1 have provided clinical benefit, particularly in renal cell and urothelial carcinoma, and have been incorporated into standard of care treatment in both localized and metastatic settings. However, a large fraction of patients do not derive benefit. Identification of patient and tumor-derived factors which associate with response have led to insights into mechanisms of response and resistance to ICI. Herein, we review current approvals and clinical development of ICI in GU malignancies and discuss exploratory biomarkers which aid in personalized treatment selection.

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“…Cholangiocarcinoma (CHOL), Kidney Chromophobe (KICH), Testicular Germ Cell Tumors (TGCT), Thyroid carcinoma (THCA), and Thymoma (THYM) were found to have more obvious immune enrichment, thus they are the so-called immune-preferred cancers. Studies have shown that immunotherapy plays an important role in the treatment of these five types of cancer ( Schott et al, 2001 ; Drake and Stein, 2018 ; Høgdall et al, 2018 ; Jakopovic et al, 2020 ; Kalavska et al, 2020 ). For these cancers, immunotherapy can achieve better prognostic effects, and our findings can provide a reference for their immunotherapy.…”

Section: Resultsmentioning

confidence: 99%

ImReLnc: Identifying Immune-Related LncRNA Characteristics in Human Cancers Based on Heuristic Correlation Optimization

et al. 2022

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Long non-coding RNAs (lncRNAs) play critical roles in cancer through gene expression and immune regulation. Identifying immune-related lncRNA (irlncRNA) characteristics would contribute to dissecting the mechanism of cancer pathogenesis. Some computational methods have been proposed to identify irlncRNA characteristics in human cancers, but most of them are aimed at identifying irlncRNA characteristics in specific cancer. Here, we proposed a new method, ImReLnc, to recognize irlncRNA characteristics for 33 human cancers and predict the pathogenicity levels of these irlncRNAs across cancer types. We first calculated the heuristic correlation coefficient between lncRNAs and mRNAs for immune-related enrichment analysis. Especially, we analyzed the relationship between lncRNAs and 17 immune-related pathways in 33 cancers to recognize the irlncRNA characteristics of each cancer. Then, we calculated the Pscore of the irlncRNA characteristics to evaluate their pathogenicity levels. The results showed that highly pathogenic irlncRNAs appeared in a higher proportion of known disease databases and had a significant prognostic effect on cancer. In addition, it was found that the expression of irlncRNAs in immune cells was higher than that of non-irlncRNAs, and the proportion of irlncRNAs related to the levels of immune infiltration was much higher than that of non-irlncRNAs. Overall, ImReLnc accurately identified the irlncRNA characteristics in multiple cancers based on the heuristic correlation coefficient. More importantly, ImReLnc effectively evaluated the pathogenicity levels of irlncRNAs across cancer types. ImReLnc is freely available at https://github.com/meihonggao/ImReLnc.

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Immunotherapy in Testicular Germ Cell Tumors

Cited by 31 publications

References 55 publications

Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes

Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes

Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

ImReLnc: Identifying Immune-Related LncRNA Characteristics in Human Cancers Based on Heuristic Correlation Optimization

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