Circulating CD8 lymphocytes predict response to atezolizumab-bevacizumab in hepatocellular carcinoma

Eur J Immunol. 2024 Feb;54(2):e2350637. doi: 10.1002/eji.202350637. Epub 2023 Dec 8.

Abstract

Due to the lack of biomarkers predictive of response to atezolizumab-bevacizumab, the standard of care for advanced HCC, we analyzed baseline and early on-treatment variation of peripheral lymphocyte populations of 37 prospective patients treated by atezolizumab-bevacizumab and in 15 prospective patients treated by sorafenib or lenvatinib (TKIs). RNAseq analysis followed by RT-PCR validation on patients-derived PBMC was also performed. At first imaging, re-evaluation 13 patients receiving atezolizumab-bevacizumab, showed an objective response, 17 stable disease, while 7 were nonresponders. Baseline CD8+ and CD8+PD-L1+ peripheral lymphocytes were lower in responders versus nonresponders (T-test, p = 0.012 and 0.004, respectively). At 3 weeks, 28 of 30 responders displayed a rise of CD8+PD1+ lymphocytes with a positive mean fold change of 4.35 (±5.6 SD), whereas 6 of 7 nonresponders displayed a negative fold change of 0.89 (±0.84 SD). These changes were not observed in patients treated by TKIs. TRIM56, TRIM16, TRIM64, and Ki67 mRNAs were validated as upregulated in responders versus nonresponders after 3 weeks after treatment start, providing possible evidence of immune activation. Baseline CD8+ and CD8+PD-L1+ peripheral lymphocytes and early changes in CD8+PD1+ lymphocytes predict response to atezolizumab-bevacizumab providing noninvasive markers to complement clinical practice in the very early phases of treatment of HCC patients.

Keywords: Biomarker; HCC; PD-L1; PD1.

MeSH terms

  • Antibodies, Monoclonal, Humanized*
  • B7-H1 Antigen
  • Bevacizumab / therapeutic use
  • Biomarkers, Tumor
  • CD8-Positive T-Lymphocytes
  • Carcinoma, Hepatocellular*
  • Humans
  • Leukocytes, Mononuclear
  • Liver Neoplasms*
  • Prospective Studies
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases

Substances

  • atezolizumab
  • Bevacizumab
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • TRIM16 protein, human
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • TRIM56 protein, human
  • Antibodies, Monoclonal, Humanized