scholarly journals MP84-13 PROGRAMMED DEATH LIGAND-1 (PD-L1) EXPRESSION STATUS IN PENILE SQUAMOUS CELL CARCINOMA TUMOR CELLS AND TUMOR INFILTRATING IMMUNE CELLS

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Jennifer Rider ◽  
Alyssa Harlow ◽  
Francesca Giunchi ◽  
Jessica Carlsson ◽  
Peter Kirrander ◽  
...  
2015 ◽  
Vol 117 (1) ◽  
pp. 118-125 ◽  
Author(s):  
Yuvaraj Sambandam ◽  
Sashank Sakamuri ◽  
Sundaravadivel Balasubramanian ◽  
Azizul Haque

2020 ◽  
pp. 107815522092260
Author(s):  
Abinav Baweja ◽  
Nataliya Mar

Introduction Prognosis for patients with lymph node positive or metastatic penile squamous cell carcinoma remains poor. Chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP regimen) is recommended as a first-line option in this cohort of patients. No standard preferred subsequent-line therapy exists for patients with relapsed or refractory penile carcinoma following TIP chemotherapy. Molecular pathogenesis of penile cancer can be subdivided into human papilloma virus-dependent and human papilloma virus-independent pathways. Recent studies have demonstrated increased expression of programmed death ligand-1 in some penile tumors, commonly those that are human papilloma virus-negative. Given the rarity of penile carcinoma in industrialized countries and lack of effective therapies, checkpoint inhibitors may be an attractive treatment option for this subset of patients. Case report We report a case of metastatic penile cancer refractory to TIP chemotherapy, with a dramatic treatment response to ipilimumab and nivolumab. Molecular profiling of this tumor showed a high programmed death ligand-1 expression, high tumor mutational burden, high microsatellite instability, and alterations in DNA mismatch repair genes. Discussion This case highlights another dimension of information that may be gained with molecular genomic profiling of penile tumors, providing insight into the biologic behavior of this neoplasm and assessing for predictive biomarkers of response to immune checkpoint inhibitors.


2009 ◽  
Vol 141 (2) ◽  
pp. 177-183 ◽  
Author(s):  
Mindy R. Figures ◽  
Jessie Wobb ◽  
Koji Araki ◽  
Tingyan Liu ◽  
Lei Xu ◽  
...  

OBJECTIVE: The current treatment for advanced head and neck squamous cell carcinoma continues to result in poor outcomes. The purpose of this study is to investigate the benefit of fibroblast growth factor 2-targeted adenovirus-mediated mutant-Rad50 (FGF2-Ad-Rad50) gene transfer in enhancing chemosensitization for head and neck squamous cell carcinoma and reducing chemotoxicity. STUDY DESIGN: Randomized controlled laboratory study. SETTING: University of Pennsylvania, Philadelphia, PA. SUBJECTS AND METHODS: Human head and neck squamous cell carcinoma tumor cells and a mouse model with human head and neck squamous cell carcinoma were used for this study. There were five mice in each study group. FGF2-fab' molecule was conjugated with an adenoviral mutant-Rad50 construct. FGF2-targeted transgene expression efficiency was evaluated in vitro. Tumor cytotoxicity and growth inhibition were examined after combined FGF2-Ad-Rad50 with cisplatin treatment in vitro and in vivo. Anti-tumor mechanisms were investigated. RESULTS: FGF2-targeted gene transfer approach significantly improved transgene expression in head and neck squamous cell carcinoma tumor cells over a nontargeted approach (207.51 ± 33.62 vs 51.44 ± 8.28, respectively). FGF2-Ad-Rad50 with cisplatin demonstrated a superior tumor suppression effect (264.5 ± 124.1 mm 3 vs 567.1 ± 267.6 mm 3 ), increased DNA double-strand breaks (1349 ± 51.67 vs 774 ± 28.56), and anti-angiogenesis (%ROI: 0.76% ± 0.38% vs 2.10% ± 1.66%) in tumor cells over nontargeted adenovirus. CONCLUSION: Combination of FGF2-Ad-Rad50 with cisplatin significantly improves anti-tumor effect by targeting DNA repair systems and tumor angiogenesis. The great benefit of this strategy supports clinical trial for novel treatment of head and neck squamous cell carcinoma.


2018 ◽  
Vol 233 (8) ◽  
pp. 6125-6134 ◽  
Author(s):  
Yuvaraj Sambandam ◽  
Purushoth Ethiraj ◽  
Jessica D. Hathaway-Schrader ◽  
Chad M. Novince ◽  
Ezhil Panneerselvam ◽  
...  

2020 ◽  
Vol 25 (4) ◽  
pp. 287-294
Author(s):  
S. I. Kutukova ◽  
N. P. Beliak ◽  
G. A. Raskin ◽  
M. S. Mukhina ◽  
Yu. V. Ivaskova ◽  
...  

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.


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