Brigette Ma (The Chinese University of Hong Kong, Hong Kong SAR China)
“Immune Checkpoint Inhibitor in the Treatment of Nasopharyngeal Carcinoma: A Clinical Overview”
– The blue dots in HE (TME lymphocytes !!)
– Co-inhibitory ICPs are inductively and have immunosuppressive fun it (early: CTLA4 dampens T-cell priming; late: PDL1 act on T-effectors in TME)What’s the evidence on NPC? (2018, Duffild at al 2018, AACTR abstract 4750 —> PDL1 is expressed in immune cells + PD-L1 is induced by LMP1Fang 2014 Oncotarget 5(23)p12189
– Oncoimmunology Zhu 2017 (intratumor PD1 is important)
– Gal-9 and TIM-3 contributes to immune evasion in NPC and canc bear reversed in vireo
– NPC Exocets (C17) induces apoptosis
– Chen et al Sci Report 7, 2017 Gal-9/TIM3 and Fox3p expression (TC/TILS) in 95 paired primary and recurrent non-keratinging NPC tumors
– 2017 ASACR abstract 646 (Siu S and KW Lo —> PD1 , PD-:2 and IDO
Diversity of TME: LAG3, GITR, and other ICP immune cells systems in 13EBV+ NPC tumors (Duffield et al 2018, Abstract 4750)
Th17 cytokines profile, upregulation of eyes activating macrophages, COX2 + IL8
PD-1 blockade everything may reinvigorate CD8 T
CTL4 (differences between IgG1 and IgG4)
J Clinc Oncology 2018 10:36(14): p1412-1418. Baylor
The last NC0CTEP mass solicitation!
7 US sites, 1HK, 1SG
– Patterns of response -spider plot
(40.9% early progress;, CR: complete disappearance of bone metastasis lasting overr 1 year
Swimmer’ split: response time and duration
“Tail end of the survival curve?
-J Clinc Oncol 2017 Dec Hsu et al
Why only 20%
-Yarchon ENJM 277; 25 Dec 21 2017
– Li YY… KW Lo. 2017; 8:14121
Defective DNA mismatch repair
Anti-PDL1
HLA-A and HLA-B —> loss either one of them has better prognosis!
-question what is “loss of heterogeneous”?
HLA antibody and HLA-B antibody
This is more similar to Charles Shwonton in (kidney clear cell carcinoma)
—> that loss of HLA/B is a better prognosis
British group (Sridharan BJC 2016). <— got to look and cheat our
alteration of immune landscape by chemo-RT in HNSCC and NPC
-increased TCr and clonality
-Siu L JCO 35, May 104-104 2017
-Nat Rev clinical Oncol 13, p202 (2016_)