Article Text

Download PDFPDF

1508 Analyzing the genomic, transcriptomic and immune landscapes associated with surface somatostatin receptor 2 (SSTR2) gene expression in nasopharyngeal carcinoma (NPC)
  1. Dara Bracken-Clarke1,
  2. Harris Krause2,
  3. Nishant Gandhi3,
  4. Phillip Walker3,
  5. Minh Phan4,5,
  6. Rusha Patel4,
  7. Heloisa Soares6,
  8. Emil Lou7,
  9. Ari VanderWalde3,
  10. James L Gulley1 and
  11. Charalampos S Floudas1
  1. 1National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
  2. 2Caris Life Sciences, Irving, TX, USA
  3. 3Caris Life Sciences, Phoenix, AZ, USA
  4. 4Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
  5. 5Sarah Cannon Research Institute at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
  6. 6Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA
  7. 7University of Minnesota, Minneapolis, MN, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background NPC is a highly invasive squamous-differentiated carcinoma, more common in east and southeast Asia, and the Epstein-Barr virus (EBV) plays a key role in its pathogenesis. Recurrent and metastatic NPC is treated with cisplatin-based chemotherapy regimens, with poor survival. SSTR2 is expressed by a spectrum of neuroendocrine neoplasms and has diagnostic and therapeutic utility as a pharmaceutical target. Many NPCs express SSTR2 on the cell surface, linked to EBV positivity. In this study, we investigated the association of SSTR2 expression and EBV status with the genomic and immune landscape of NPC.

Methods 198 NPC specimens were tested at Caris Life Sciences (Phoenix, AZ) with NextGen Sequencing of DNA (592-gene panel or whole exome [WES]) and RNA (whole transcriptome). EBV status (EBV+/-) was defined using WES and EBER ISH. PD-L1 expression (22C3; Positive (+): TPS ≥1%) was assessed by IHC. A combination of IHC, NGS, and fragment analysis was used to assess deficient mismatch repair status (dMMR/MSI). Tumors were stratified as SSTR2-High (H) and -Low (L) per top and bottom quartile expression of SSTR2, respectively; or by EBV positivity. Transcriptome data were analyzed for a signature predictive of response to immunotherapy (T-cell inflamed score). Immune cell fractions were estimated using quanTIseq. Mann-Whitney U, Fisher’s Exact and χ2 tests were applied as appropriate with p-values adjusted for multiple comparisons (p < 0.05).

Results 60.4% of NPC were EBV+ (98/165) and the prevalence of SSTR2-H status was significantly associated with EBV+compared to SSTR2-L status (90.5% vs 7.3%, p < 0.). PD-L1 positivity was highly prevalent in NPC, without significant difference observed between SSTR2-H vs -L tumors (97.9% vs 86.5%). dMMR/MSI-H was observed in 0.38% (1/261) of tumors. A significantly higher fraction of SSTR2-H (vs SSTR2-L) tumors were T-cell inflamed (75% vs 6%, p < 0.05; figure 1). SSTR2-H tumors (vs SSTR2-L) also had significantly elevated M1 macrophages (8.1% vs 3.5%), B-cells (13.0% vs 5.4%) and Tregs(7.3% vs 2.2%) infiltrate and significantly reduced neutrophil infiltrate (2.4% vs 4.9%) (all p < 0.05). When segmenting NPC by EBV status, EBV­- NPC had a higher prevalence of pathogenic PIK3CA mutations as compared to EBV+ NPC (16.9% vs 0%, p < 0.).

Conclusions In NPC, SSTR2 expression was positively associated with EBV positivity and with an inflamed, immunogenic tumor microenvironment. Thus, in SSTR2-H NPC, immunotherapy and also SSTR2-directed strategies may be appropriate therapeutic strategies. In EBV- NPC, PIK3CA-directed therapy merits further investigation.

Abstract 1508 Figure 1

Prevalence of T-cell inflamed tumors across SSTR2 expression qurtiles

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.