Immune checkpoint blockade in esophageal squamous cell carcinoma: is it ready for prime time?

Pectasides, Eirini

doi:10.21037/jtd.2018.02.74

Cited by 4 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, selecting drugs based on genomics data has led to promising results in early studies on personalized and targeted therapy. Some of targeted drugs have been utilized in ESCC, such as Gefitinib 3 (an EGFR inhibitor), Dovitinib 4 (an FGFR1 inhibitor), and PD-L1 blockers 5 . However, only a small subset of patients has long-term benefit from these target therapies, which raises the question whether the substantial intra-tumor heterogeneity (ITH) of cancer cells or tumor immune microenvironment such as tumor-infiltrating lymphocytes and derived T cell receptor (TCR) repertoire are responsible for the differences.…”

Section: Introductionmentioning

confidence: 99%

Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma

et al. 2019

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) ranks fourth among cancer-related deaths in China due to the lack of actionable molecules. We performed whole-exome and T-cell receptor (TCR) repertoire sequencing on multi-regional tumors, normal tissues and blood samples from 39 ESCC patients. The data revealed 12.8% of ERBB4 mutations at patient level and functional study supported its oncogenic role. 18% of patients with early BRCA1 /2 variants were associated with high-level contribution of signature 3, which was validated in an independent large cohort ( n = 508). Furthermore, knockdown of BRCA1 /2 dramatically increased sensitivity to cisplatin in ESCC cells. 5% of patients harbored focal high-level amplification of CD274 that led to massive expression of PD-L1, and might be more sensitive to immune checkpoint blockade. Finally, we found a tight correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH). Collectively, we reveal high-level ITH in ESCC, identify several potential actionable targets and may provide novel insight into ESCC treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Recent studies have reported the association of the densities of CD4+ and CD8+ cells in the tumor microenvironment to the tumor growth inhibition in the preclinical experiments(Okuyama et al, ) and also, good prognosis and improved survival of cancer patients. (Han et al, ; Pectasides, ; Sznurkowski, Żawrocki, Emerich, & Biernat, )…”

Section: Discussionmentioning

confidence: 99%

“…( Okuyama et al, ) In recent studies, the densities of CD4+ and CD8+ cells in the tumor microenvironment were revealed to be associated with tumor growth inhibition in the preclinical experiments(Okuyama et al, ) and also, good prognosis and improved survival of cancer patients. (Han et al, ; Pectasides, ; Sznurkowski et al, ) Løbner et al . have reported not only Immulina® can significantly enhance CD4+ and CD8+ T cell proliferation in response to specific antigens, but also, it can induce these T cell proliferation per se in a dose‐dependent manner in vitro.…”

Section: Discussionmentioning

confidence: 99%

Spirulina extract enriched for Braun‐type lipoprotein (Immulina®) for inhibition of 4T1 breast tumors' growth and metastasis

Kefayat

Ghahremani

Safavi

et al. 2019

Phytotherapy Research

View full text Add to dashboard Cite

Spirulina platensis extracts have exhibited considerable anti-cancer effects. To investigate the efficacy of the Spirulina extract enriched for Braun-type lipoprotein (Immulina®) for breast cancer treatment, 4T1 breast tumor-bearing mice were treated with 40 mg/kg Immulina® daily and the tumors' growth and metastasis were assessed. Also, CD4, CD8, and CD56 staining were performed to investigate the Immulina® effect on the immune cells' recruitment to the tumors by immunohistochemistry. Immulina® could significantly (P < 0.001) inhibit 4T1 breast tumors' growth. Immulina®-treated group exhibited a 63% decrease in the tumors' volume in comparison with control (P < 0.001). Also, Immulina® could significantly (P < 0.001) decrease metastatic burden at the vital organs as 68% and 61% decrease in the liver and lungs metastatic colonies were observed, respectively. Also, Immulina® could increase mean survival time of the tumor-bearing mice for 29 days.The Spirulina-treated mice tumors contained significantly more infiltrated NK, CD4+, and CD8+ T lymphocytes in comparison with control. Taking together, Immulina® can be a safe anti-cancer supplement with the ability to cause direct apoptosis to the cancer cells and activate the immune system against tumor. This supplement with natural origin seems to have bright future to help breast cancer patients.

show abstract

“…Another well-understood case is chronic myeloid leukemia, in which mutant forms of the BCR-ABL fusion protein have been implicated in the relapse of disease under imatinib treatment [50,51,52]. In ESCC, heterogeneous amplifications of EGFR , FGFR1 , and PD-L1 have been reported [42,43,44], accounting partially for the unsatisfactory efficacy of targeting such genomic lesions [53,54,55]. Spatial genomic heterogeneity, therefore, greatly challenges both accurate diagnosis and efficient cancer treatment.…”

Section: Intratumor Heterogeneitymentioning

confidence: 99%

Biological Significance of Tumor Heterogeneity in Esophageal Squamous Cell Carcinoma

Lin¹,

Lin²

2019

Cancers

View full text Add to dashboard Cite

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy, with hitherto dismal clinical outcome. Genomic analyses of patient samples reveal a complex heterogeneous landscape for ESCC, which presents in both intertumor and intratumor forms, manifests at both genomic and epigenomic levels, and contributes significantly to tumor evolution, drug resistance, and metastasis. Here, we review the important molecular characteristics underlying ESCC heterogeneity, with an emphasis on genomic aberrations and their functional contribution to cancer evolutionary trajectories. We further discuss how novel experimental tools, including single-cell sequencing and three-dimensional organoids, may advance our understanding of tumor heterogeneity. Lastly, we suggest that deciphering the mechanisms governing tumor heterogeneity holds the potential to developing precision therapeutics for ESCC patients.

show abstract

Immune checkpoint blockade in esophageal squamous cell carcinoma: is it ready for prime time?

Cited by 4 publications

References 20 publications

Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma

Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma

Spirulina extract enriched for Braun‐type lipoprotein (Immulina®) for inhibition of 4T1 breast tumors' growth and metastasis

Biological Significance of Tumor Heterogeneity in Esophageal Squamous Cell Carcinoma

Contact Info

Product

Resources

About