Dear Editor,
We greatly appreciate the insightful correspondence to our editorial from the authors [
1]. We fully agree with the authors that this study warrants further validation of the immune signature score (ISS) and its simplified version (ISS10) in larger cohorts, representing more non-Asian patients and metabolic (liver) diseases to confirm their clinical utility [
2,
3]. We also agree that adoption of emerging technologies such as liquid biopsy will enhance their clinical applicability and enable exploration of logistically most sensible assay modalities [
4]. In addition, the single-cell and spatial omic profiling assays will provide insight into the cellular sources of ISS/ISS10 in the hepatocellular carcinoma (HCC) tumor immune microenvironment [
5]. Furthermore, integration with the rapidly evolving digital pathology methods may enhance their applicability in broader clinical contexts and environment with limited access to such omics assays [
6].
It is encouraging to observe association of ISS/ISS10 with responses to various immune checkpoint inhibitor -based regimens that involve anti-PD-1, anti-PD-L1, anti-CTLA-4, and anti-VEGF currently approved for the treatment of advanced HCC [
7]. Further assessment for the new classes of immunologic agents such as anti-TIGIT will be needed in future studies [
8]. Their response-predictive capability should be evaluated for each individual agent and combinatory regimen, and therefore, acquisition of biospecimens, particularly tissue samples, will be critical, perhaps along with other candidate biomarkers for their costeffective assessment. In summary, we anticipate further evaluation of ISS/ISS10 toward their clinical translation to improve the management and treatment outcomes of patients with HCC.
FOOTNOTES
-
Authors’ contribution
HK drafted the manuscript. YH reviewed and finalized the manuscript.
-
Conflicts of Interest
HK served as a consultant on advisory boards from Takeda and Bayer. YH is shareholder for Alentis Therapeutics and Espervita Therapeutics, advisory for Helio Genomics, Espervita Therapeutics, Elevar Therapeutics, and Roche Diagnostics.
Abbreviations
metabolic dysfunction-associated steatotic liver disease
REFERENCES
- 1. Lee SH, Yim SY, Kim JH, Lee SS, Kaseb AO, Lee JS. Correspondence to editorial 1 on “Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: insights from the IMbrave150 Trial”. Clin Mol Hepatol 2025;31:e81-e83.
- 2. Ock CY, Hwang JE, Keam B, Kim SB, Shim JJ, Jang HJ, et al. Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers. Nat Commun 2017;8:1050.
- 3. Yim SY, Lee SH, Baek SW, Sohn B, Jeong YS, Kang SH, et al. Genomic biomarkers to predict response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma: insights from the IMbrave150 trial. Clin Mol Hepatol 2024;30:807-823.
- 4. Lee YT, Fujiwara N, Yang JD, Hoshida Y. Risk stratification and early detection biomarkers for precision HCC screening. Hepatology 2023;78:319-362.
- 5. Dhanasekaran R, Suzuki H, Lemaitre L, Kubota N, Hoshida Y. Molecular and immune landscape of hepatocellular carcinoma to guide therapeutic decision-making. Hepatology 2023 Jun 12;doi: 10.1097/HEP.0000000000000513. Epub ahead of print.
- 6. Zeng Q, Klein C, Caruso S, Maille P, Allende DS, Mínguez B, et al. Artificial intelligence-based pathology as a biomarker of sensitivity to atezolizumab-bevacizumab in patients with hepatocellular carcinoma: a multicentre retrospective study. Lancet Oncol 2023;24:1411-1422.
- 7. Gordan JD, Kennedy EB, Abou-Alfa GK, Beal E, Finn RS, Gade TP, et al. Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update. J Clin Oncol 2024;42:1830-1850.
- 8. Butterfield LH, Najjar YG. Immunotherapy combination approaches: mechanisms, biomarkers and clinical observations. Nat Rev Immunol 2024;24:399-416.
Citations
Citations to this article as recorded by
