原文題目(出處)： Cell genomics and immunosuppressive biomarker expression influence PD-L1 immunotherapy treatment responses in HNSCC-a computational study
原文作者姓名： Amber M. Bates, BS Emily A. Lanzel, DDS, MS Fang Qian, PhD
Taher Abbasi, ME, MBA Shireen Vali, PhD
Kim A. Brogden, PhD
通訊作者學校： Iowa Institute for Oral Health Research, College of Dentistry,University of Iowa, Iowa City, IA, USA 報告者姓名(組別)： 蔡宗哲(int.C)
報告日期： 2017/10/05 內文：
1. study objectives:
Demonstrating a need for a more accurate method to identify those who will respond before immunotherapy.
PD-1&PD-L1: Overexpression of PD-L1 on tumor cells skews anti-tumor immunity by impeding anti-tumor CD8+ T-cell function through inhibition of T-cell proliferation, reduction of T-cell survival, inhibition of cytokine release, and promotion of T-cell apoptosis.
所以若可阻斷 PD-1 或是 PD-L1 即可使 T-cell 有功能(目前大多數藥物都是抑制 PD-1，如:
Nivolumab，Pembrolizumab；抑制 PD-L1 的臨床藥物有 Atezolizumab 和 Avelumab) 目前這兩種免疫藥物的 objective response rate 最高只有 24.8%
biomarkers and that these profiles can be used to predict clinical responses in patients.
3. Materials and methods A. Sitmulation model
i. Cell line:SCC4,SCC15,SCC25→exam exomes from each cell line for deleterious gene mutations
ii. Simulation models:create predictive computational simulation models
iii. The models did not contain cell line - specific deleterious gene mutation profiles and were simulated to reach a homeostatic steady state, which served as the control baseline for the biomarkers of interest.
iv. Specific deleterious gene mutation profiles were converted into a computational format and annotated into the HNSCC cancer network, simulated to induce the cell line - specific cancer disease states, and used to predict the expression of 24 chemokines and immunosuppressive biomarkers.
B. Immunosuppressive biomarkers
i. 9 chemokines can trafficking dendritic cells into tumor microenviroment ii. 14 biomarkers act as immunosuppressive mediatiors
iii. Calculate the index with ([D - C]/C)*100, where C is the absolute value of the nontumorigenic baseline control (mM), and D is the absolute value of the biomarker obtained in the cell lineespecific cancer state network(mM)
C. Predicted response to PD-L1 immunotherapy
i. Use calculated index to sort cell lines into those that would respond to PD-L1 immunotherapy and those that would not
SCC4:TP53, CDK6, CCND1, NF1
SCC15 :EGFR, PIK3 CB, DUSP22, MAP3 K1 SCC25:TP53, CDKN2 A, LAMTOR5.
5. Discussion
A. This study determined the expression levels of 24 chemokines and immunosuppressive biomarkers.
B. SCC15 and SCC25, cell lines originally from patients with HNSCC, would likely respond to PD-L1 immunotherapy treatment.
C. SCC4, a cell line from a patient with HNSCC, would not likely respond to PD-L1 immunotherapy treatment
D. Why choose PD-L1?
It is expressed in 46%-100% of human HNSCC biopsy specimens across multiple primary sites
E. These three step cut-offs has been used to predict PD-1 responder on small cell lung cancer therapy.
6. Conclusion
These models will be able to complement IHC results or provide effective where IHC is unfeasible, identify factors that influence PD-L1 expression, and serve as a clinical decision support system to classify patients into those that would respond to PD-L1
immunotherapy and those that would not base on patient’s deleterious gene mutation profile.
題號 題目
1 Which is true below about head and neck SCC ? (A) Usually, it can be detected at early stage
(B) HNSCC has no connection with factors such as gender,age,race (C) Treatment of HNSCC includes surgery,radio
therapy,chemotherapy,gene therapy and immunotherapy
(D) Distant metastasis is common in HNSCC and usually affects the choice of therapy
答案 (C )
出處： Burket’s Oral Medicine 11th edition,Chapter 7
題號 題目
2 Which description below about PD-1 and PD-L1 is wrong ?
(A) Overexpression of PD-L1 on tumor cell decrease T-cell function (B) We have develop sufficient method to identify patients who are
adequate to immunotherapy of HNSCC
(C) Nivolumab and Pembrolizumab inhibits PD-1 function (D) PD-L1 express in most of HNSCC biopsy specimens 答案
(B )
參考本篇研究
目前臨床上投藥有效的比率最高為 24.8%( Pembrolizumab)並不高
