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Background <p>We previously reported a phase II Kyoto trial for platinum-resistant ovarian cancer (n = 20) using nivolumab (anti-programmed cell death-1 [PD-1] antibody). We evaluated the associations between clinical outcomes and transcriptomics and T and B cell clonality from tumor and blood cells.</p> Methods <p>We analyzed gene expression microarray with pre- and post-treatment peripheral blood mononuclear cells, α- and <i>β</i>-chain of T cell receptor (TCR) repertoires, and immunoglobulin G (IgG) and M of B cell receptor (BCR) repertoires in 61 samples from 19 patients. Shannon–Weaver diversity scores of the TCR and BCR repertoires were compared between responders and non-responders. RNA sequencing analyzed gene expression and fusion genes in tumor samples (n = 17).</p> Results <p>BCR repertoire analyses of post-/pre-treatment ratios in four responders (two patients with complete response (CR), one with partial response, and one with stable disease near to CR) revealed significantly decreased BCR-IgG repertoires diversity versus non-responders (Shannon–Weaver index, median 0.84 vs. 1.04, p &lt; 0.05); the diversity of BCR-IgG repertoires recovered over 100&#xa0;days. More than two passenger fusion genes were detected in six of the seven responders, whereas eight of the ten non-responders lacked fusion genes. The antitumor response significantly correlated with the number of fusion genes (p = 0.0006). Pathway analyses consistently identified immune-related processes, including cytokine-cytokine receptor interactions, neutrophil degranulation, and immunoregulatory interactions in both responders and tumors with high fusion gene counts.</p> Conclusion <p>Transient oligoclonal expansion of B cells and passenger fusion genes might serve as predictive biomarkers of response to PD-1 blockade in ovarian cancer.</p>

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Oligoclonal B cell expansion and passenger fusion genes predict response to Nivolumab in recurrent ovarian cancer: phase II Kyoto trial

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • Ryusuke Murakami,
  • Junzo Hamanishi,
  • J. B. Brown,
  • Yuko Hosoe,
  • Takuma Kobayashi,
  • Teppei Konishi,
  • Taito Miyamoto,
  • Rin Mizuno,
  • Mana Taki,
  • Koji Yamanoi,
  • Ken Yamaguchi,
  • Masaki Mandai

摘要

Background

We previously reported a phase II Kyoto trial for platinum-resistant ovarian cancer (n = 20) using nivolumab (anti-programmed cell death-1 [PD-1] antibody). We evaluated the associations between clinical outcomes and transcriptomics and T and B cell clonality from tumor and blood cells.

Methods

We analyzed gene expression microarray with pre- and post-treatment peripheral blood mononuclear cells, α- and β-chain of T cell receptor (TCR) repertoires, and immunoglobulin G (IgG) and M of B cell receptor (BCR) repertoires in 61 samples from 19 patients. Shannon–Weaver diversity scores of the TCR and BCR repertoires were compared between responders and non-responders. RNA sequencing analyzed gene expression and fusion genes in tumor samples (n = 17).

Results

BCR repertoire analyses of post-/pre-treatment ratios in four responders (two patients with complete response (CR), one with partial response, and one with stable disease near to CR) revealed significantly decreased BCR-IgG repertoires diversity versus non-responders (Shannon–Weaver index, median 0.84 vs. 1.04, p < 0.05); the diversity of BCR-IgG repertoires recovered over 100 days. More than two passenger fusion genes were detected in six of the seven responders, whereas eight of the ten non-responders lacked fusion genes. The antitumor response significantly correlated with the number of fusion genes (p = 0.0006). Pathway analyses consistently identified immune-related processes, including cytokine-cytokine receptor interactions, neutrophil degranulation, and immunoregulatory interactions in both responders and tumors with high fusion gene counts.

Conclusion

Transient oligoclonal expansion of B cells and passenger fusion genes might serve as predictive biomarkers of response to PD-1 blockade in ovarian cancer.