Highlights
- •The ‘HOT’ score allows to identify immunologically active ‘hot’ tumours.
- •Patients with hot tumours treated by PD1/PD-L1 inhibitors had improved survival.
- •The immunologically ‘hot’ phenotype is stable between biopsy and surgical specimen.
- •The HOT score is a promising biomarker evaluable from real-life FFPE samples.
Abstract
Introduction
Identification of tumours harbouring an overall active immune phenotype may help for
selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and
non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective
was to develop a reliable and stable scoring system to identify those immunologically
active tumours.
Methods
Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically
active tumours. Validation of the ‘HOT’ score was done in 40 HNSCC and 992 NSCLC.
Stability of the ‘HOT’ score was tested in paired HNSCC samples from diagnostic biopsies
versus surgically resected specimens, untreated versus recurrent samples, and pre-versus
post-cetuximab samples in a total of 76 patients. The association between the ‘HOT’
score with overall survival (OS) and progression-free survival (PFS) was tested in
184 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors.
Results
A 27-gene expression based ‘HOT’ score was correlated with: (i) PD-L1 and IDO1 expression,
(ii) TCD8 infiltrate and (iii) activation of the IFN-γ pathway. The HOT score concordance
when comparing diagnostic biopsies and surgically resected specimens was higher than
in untreated samples versus recurrent or pre-versus post-cetuximab samples. In 102
and 82 patients with HNSCC or NSCLC treated with PD-1/PD-L1 inhibitors, the HOT score
was associated with an improved OS and PFS in multivariate analysis.
Conclusion
The ‘HOT’ score is a simple and robust approach to identify real-world patients with
HNSCC and NSCLC immunologically active tumours who may benefit from PD-1/PD-L1 inhibitors.
Keywords
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Article info
Publication history
Published online: August 26, 2022
Accepted:
June 17,
2022
Received in revised form:
May 25,
2022
Received:
March 2,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
