Abstract 186P
Background
LELC is an Epstein-Barr Virus (EBV)-associated epithelial tumour histologically indistinguishable from NPC. Due to its rarity, characteristics of pulmonary LELC (PLELC) are poorly understood, and optimal treatment is poorly defined. We report the largest spatial transcriptomic and mIHC/mIF-based comparative analysis of PLELC and NPC, with an aim to characterise their tumour microenvironment (TME), and identify potential prognostic biomarkers and therapeutic targets.
Methods
We examined archival formalin-fixed paraffin embedded (FFPE) PLELC specimens from 39 patients (2000-2019) from National Cancer Centre Singapore and Singapore General Hospital. PLELC samples underwent IHC staining of SSTR2 antibody to assess for SSTR2 expression. Laser capture microdissection (LCM) followed by whole transcriptomic sequencing was also carried out for PLELC samples and compared against NPC datasets, while mIF-based (Vectra 3.0) comparisons were made for NPC and PLELC.
Results
In 20 out of 39 (59%) LELC samples, SSTR2 was positive, with 48% positivity in stage I-III and 75% in stage IV LELC. 59 differentially expressed genes were identified in PLELC compared to NPC (p<0.01) in the tumour epithelial compartment. Preferentially Expressed Antigen of Melanoma (PRAME), a cancer testis antigen with potential for targeting alongside immunotherapy, was particularly highly upregulated (p<0.01). The immune markers CD4, CD8, PD1 and CD137 expression was significantly higher in PLELC, while expression of CD20 was higher in NPC by mIF analyses.
Conclusions
In comparison to NPC, PLELC tumours exhibit an inflammatory TME, with abundant CD4 and CD8 T cells and significantly higher CD137 and PD1 expression. The elevated levels of PRAME, linked to poorer prognosis, along with high expression of both SSTR2 and PRAME in PLELC show promise as potential therapeutic targets.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Medical Research Council.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
122P - Practice patterns and treatment outcomes of molecular tumour board (MTB)-based personalized cancer therapies: A single-center experience
Presenter: Florian Moik
Session: Poster session 08
123P - Pan-cancer homologous recombination deficiency (HRD) evaluation in patients enrolled in a routine molecular screening program
Presenter: Paula Romero-Lozano
Session: Poster session 08
124P - Incidence of activating frameshift and nonsense mutations in clinically actionable oncogenes
Presenter: Sjors Kas
Session: Poster session 08
125P - Comparison of microarray and next-generation sequencing-based approaches for detection of homologous recombination deficiency
Presenter: Caleb Kidwell
Session: Poster session 08
126P - Genomic landscape and prognostic impact of HER2 low-expressing tumors
Presenter: Aditya Shreenivas
Session: Poster session 08
127P - Clinical utility of circulating tumor DNA (ctDNA) next generation sequencing (NGS) to inform treatment decisions for patients (pts) with advanced solid tumors
Presenter: Diego Gomez Puerto
Session: Poster session 08
128P - Whole blood transcriptomics identifies transcriptional patterns linked to outcomes in patients receiving immune checkpoint inhibitors
Presenter: Sara Hone Lopez
Session: Poster session 08
129P - Integrating large data to unveil vulnerabilities for patients with hot tumors resistant to checkpoint inhibition
Presenter: Anlin Li
Session: Poster session 08
130P - Ipilimumab plus nivolumab (Ipi+Nivo) in patients with tumors harboring high tumor mutational burden or load (TMB/TML-H): Results from the Drug Rediscovery Protocol (DRUP)
Presenter: Soemeya Haj Mohammad
Session: Poster session 08
131P - Systemic immune-inflammation index and overall survival with checkpoint inhibitors
Presenter: Oliver Kennedy
Session: Poster session 08