scholarly journals Rapid regression of microsatellite instability-high/programmed cell death ligand 1-negative recurrent endometrial carcinoma by immune checkpoint blockade with pembrolizumab: A case report and literature review

2020 ◽  
Vol 32 ◽  
pp. 100553
Author(s):  
Akihiro Takeda ◽  
Wataru Koike ◽  
Kazuko Watanabe
Keyword(s):  
Cell Death ◽  
Case Report ◽  
Programmed Cell Death ◽  
Literature Review ◽  
Microsatellite Instability ◽  
Endometrial Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Rapid Regression

scholarly journals Immune-Checkpoint Blockade Therapy in Lymphoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5456 ◽  
Author(s):  
Ayumi Kuzume ◽  
SungGi Chi ◽  
Nobuhiko Yamauchi ◽  
Yosuke Minami
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Malignant Lymphoma ◽  
Hodgkin Lymphoma ◽  
Immune Checkpoint ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Host Immune System ◽  
Cell Death Protein

Tumor cells use immune-checkpoint pathways to evade the host immune system and suppress immune cell function. These cells express programmed cell-death protein 1 ligand 1 (PD-L1)/PD-L2, which bind to the programmed cell-death protein 1 (PD-1) present on cytotoxic T cells, trigger inhibitory signaling, and reduce cytotoxicity and T-cell exhaustion. Immune-checkpoint blockade can inhibit this signal and may serve as an effective therapeutic strategy in patients with solid tumors. Several trials have been conducted on immune-checkpoint inhibitor therapy in patients with malignant lymphoma and their efficacy has been reported. For example, in Hodgkin lymphoma, immune-checkpoint blockade has resulted in response rates of 65% to 75%. However, in non-Hodgkin lymphoma, the response rate to immune-checkpoint blockade was lower. In this review, we evaluate the biology of immune-checkpoint inhibition and the current data on its efficacy in malignant lymphoma, and identify the cases in which the treatment was more effective.

scholarly journals The Role of Immune Checkpoint Blockade in the Hepatocellular Carcinoma: A Review of Clinical Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Muhammet Ozer ◽  
Andrew George ◽  
Suleyman Yasin Goksu ◽  
Thomas J. George ◽  
Ilyas Sahin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Cell Death ◽  
Liver Cancer ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Primary Liver Cancer ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Line Treatment

The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.

Enhancing KDM5A and TLR activity improves the response to immune checkpoint blockade

2020 ◽  
Vol 12 (560) ◽  
pp. eaax2282 ◽  
Author(s):  
Liangliang Wang ◽  
Yan Gao ◽  
Gao Zhang ◽  
Dan Li ◽  
Zhenda Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
T Cell Activation ◽  
Immune Checkpoint ◽  
Cell Activation ◽  
Gene Signature ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Tensin Homolog ◽  
Cancer Models

Immune checkpoint blockade (ICB) therapies are now established as first-line treatments for multiple cancers, but many patients do not derive long-term benefit from ICB. Here, we report that increased amounts of histone 3 lysine 4 demethylase KDM5A in tumors markedly improved response to the treatment with the programmed cell death protein 1 (PD-1) antibody in mouse cancer models. In a screen for molecules that increased KDM5A abundance, we identified one (D18) that increased the efficacy of various ICB agents in three murine cancer models when used as a combination therapy. D18 potentiated ICB efficacy through two orthogonal mechanisms: (i) increasing KDM5A abundance, which suppressed expression of the gene PTEN (encoding phosphatase and tensin homolog) and increased programmed cell death ligand 1 abundance through a pathway involving PI3K-AKT-S6K1, and (ii) activating Toll-like receptors 7 and 8 (TLR7/8) signaling pathways. Combination treatment increased T cell activation and expansion, CD103+ tumor-infiltrating dendritic cells, and tumor-associated M1 macrophages, ultimately enhancing the overall recruitment of activated CD8+ T cells to tumors. In patients with melanoma, a high KDM5A gene signature correlated with KDM5A expression and could potentially serve as a marker of response to anti–PD-1 immunotherapy. Furthermore, our results indicated that bifunctional agents that enhance both KDM5A and TLR activity warrant investigation as combination therapies with ICB agents.

STAT6 correlates with response to immune checkpoint blockade therapy and predicts worse survival in thyroid cancer

2020 ◽  
Vol 14 (11) ◽  
pp. 955-967
Author(s):  
Li Wang ◽  
Shijia Yu ◽  
Yelin Yin ◽  
Ying Hao
Keyword(s):  
Cell Death ◽  
Thyroid Cancer ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Prognostic Biomarker ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Signal Transducer

Aim: The signal transducer and activator of transcription (STAT) family has been documented. However, the role of STATs in thyroid cancer was not fully studied. Materials & methods: A survival analysis of STATs was performed. The function modulated by STAT6 was examined. The role of STAT6 in cancer immune infiltrates and immune checkpoint blockade molecules was investigated. Results: Only low STAT6 expression correlated with worse survival. STAT6 is involved in cell cycle, cell adhesion, apoptosis and notch signaling pathways. STAT6 was significantly positively associated with immune infiltration of B cells, CD4+ T cells, neutrophils, macrophages, dendritic cells and the immune checkpoint blockade molecules programmed cell death-ligand 1, programmed cell death-ligand 2 and cytotoxic T-lymphocyte-associated protein 4. Conclusion: STAT6 may act as a prognostic biomarker and provide useful information for immunotherapy in thyroid carcinoma.

scholarly journals Comprehensive analysis of cutaneous and uveal melanoma liver metastases

2020 ◽  
Vol 8 (2) ◽  
pp. e001501
Author(s):  
Esmee P Hoefsmit ◽  
Elisa A Rozeman ◽  
Trieu My Van ◽  
Petros Dimitriadis ◽  
Oscar Krijgsman ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Liver Metastases ◽  
Uveal Melanoma ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Metastatic Site ◽  
Immune Infiltration

BackgroundThe profound disparity in response to immune checkpoint blockade (ICB) by cutaneous melanoma (CM) and uveal melanoma (UM) patients is not well understood. Therefore, we characterized metastases of CM and UM from the same metastatic site (liver), in order to dissect the potential underlying mechanism in differential response on ICB.MethodsTumor liver samples from CM (n=38) and UM (n=28) patients were analyzed at the genomic (whole exome sequencing), transcriptional (RNA sequencing) and protein (immunohistochemistry and GeoMx Digital Spatial Profiling) level.ResultsComparison of CM and UM metastases from the same metastatic site revealed that, although originating from the same melanocyte lineage, CM and UM differed in somatic mutation profile, copy number profile, tumor mutational burden (TMB) and consequently predicted neoantigens. A higher melanin content and higher expression of the melanoma differentiation antigen MelanA was observed in liver metastases of UM patients. No difference in B2M and human leukocyte antigen-DR (HLA-DR) expression was observed. A higher expression of programmed cell death ligand 1 (PD-L1) was found in CM compared with UM liver metastases, although the majority of CM and UM liver metastases lacked PD-L1 expression. There was no difference in the extent of immune infiltration observed between CM and UM metastases, with the exception of a higher expression of CD163 (p<0.0001) in CM liver samples. While the extent of immune infiltration was similar for CM and UM metastases, the ratio of exhausted CD8 T cells to cytotoxic T cells, to total CD8 T cells and to Th1 cells, was significantly higher in UM metastases.ConclusionsWhile TMB was different between CM and UM metastases, tumor immune infiltration was similar. The greater dependency on PD-L1 as an immune checkpoint in CM and the identification of higher exhaustion ratios in UM may both serve as explanations for the difference in response to ICB. Consequently, in order to improve current treatment for metastatic UM, reversal of T cell exhaustion beyond programmed cell death 1 blockade should be considered.

scholarly journals An unsuspected complication with immune checkpoint blockade: a case report

2018 ◽  
Vol 12 (1) ◽  
Author(s):  
Lucia Carril-Ajuria ◽  
Elisabeth Jiménez-Aguilar ◽  
Carlos Gómez-Martín ◽  
Carmen Díaz-Pedroche
Keyword(s):  
Case Report ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade
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