RGD Reference Report - Immune Activation and Benefit From Avelumab in EBV-Positive Gastric Cancer. - Rat Genome Database

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Immune Activation and Benefit From Avelumab in EBV-Positive Gastric Cancer.

Authors: Panda, Anshuman  Mehnert, Janice M  Hirshfield, Kim M  Riedlinger, Greg  Damare, Sherri  Saunders, Tracie  Kane, Michael  Sokol, Levi  Stein, Mark N  Poplin, Elizabeth  Rodriguez-Rodriguez, Lorna  Silk, Ann W  Aisner, Joseph  Chan, Nancy  Malhotra, Jyoti  Frankel, Melissa  Kaufman, Howard L  Ali, Siraj  Ross, Jeffrey S  White, Eileen P  Bhanot, Gyan  Ganesan, Shridar 
Citation: Panda A, etal., J Natl Cancer Inst. 2018 Mar 1;110(3):316-320. doi: 10.1093/jnci/djx213.
RGD ID: 124715448
Pubmed: PMID:29155997   (View Abstract at PubMed)
PMCID: PMC6658862   (View Article at PubMed Central)
DOI: DOI:10.1093/jnci/djx213   (Journal Full-text)

Response to immune checkpoint therapy can be associated with a high mutation burden, but other mechanisms are also likely to be important. We identified a patient with metastatic gastric cancer with meaningful clinical benefit from treatment with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab. This tumor showed no evidence of high mutation burden or mismatch repair defect but was strongly positive for presence of Epstein-Barr virus (EBV) encoded RNA. Analysis of The Cancer Genome Atlas gastric cancer data (25 EBV+, 80 microsatellite-instable [MSI], 310 microsatellite-stable [MSS]) showed that EBV-positive tumors were MSS. Two-sided Wilcoxon rank-sum tests showed that: 1) EBV-positive tumors had low mutation burden (median = 2.07 vs 3.13 in log10 scale, P < 10-12) but stronger evidence of immune infiltration (median ImmuneScore 2212 vs 1295, P < 10-4; log2 fold-change of CD8A = 1.85, P < 10-6) compared with MSI tumors, and 2) EBV-positive tumors had higher expression of immune checkpoint pathway (PD-1, CTLA-4 pathway) genes in RNA-seq data (log2 fold-changes: PD-1 = 1.85, PD-L1 = 1.93, PD-L2 = 1.50, CTLA-4 = 1.31, CD80 = 0.89, CD86 = 1.31, P < 10-4 each), and higher lymphocytic infiltration by histology (median tumor-infiltrating lymphocyte score = 3 vs 2, P < .001) compared with MSS tumors. These data suggest that EBV-positive low-mutation burden gastric cancers are a subset of MSS gastric cancers that may respond to immune checkpoint therapy.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CD8AHumanEpstein-Barr virus infectious disease  HEP associated with stomach cancer and mRNA:increased expression:stomach (human)RGD 

Objects Annotated

Genes (Homo sapiens)
CD8A  (CD8 subunit alpha)


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