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Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial

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Abstract

Purpose

Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy.

Methods

We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK−PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival.

Results

CD8+ T cells, PD-L1+ cells, and PANCK−PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK−PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively).

Conclusions

Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK−PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy.

Clinical trial registration

ClinicalTrials. gov identifier: NCT03816553, January 25, 2019.

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Availability of data and materials

The key raw data have been recorded at Research Data Deposit public platform (http://www.researchdata.org.cn) with number RDDB2021891367. The data are available from Research Data Deposit but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of the Research Data Deposit public platform.

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Funding

No funding was received for conducting this study.

Author information

Author notes

  1. Yin Wang and Yuerong Lai have contributed equally.

  2. Chongjie Tong and Xin Huang have contributed equally.

Authors and Affiliations

  1. Department of Gynecologic Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, People’s Republic of China

    Yin Wang, Yuerong Lai, Hongyu Peng, Zhimin Liu, Chongjie Tong & Xin Huang

  2. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People’s Republic of China

    Shumei Yan

  3. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People’s Republic of China

    Yin Wang, Yuerong Lai, Hongyu Peng, Shumei Yan, Zhimin Liu, Chongjie Tong & Xin Huang

Authors
  1. Yin Wang
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  2. Yuerong Lai
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  3. Hongyu Peng
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Contributions

Conceptualization: Yin Wang, Chongjie Tong and Xin Huang; methodology: Yin Wang and Xin Huang; formal analysis and investigation: Yuerong Lai and Shumei Yan; writing—original draft preparation: Yin Wang and Hongyu Peng; writing—review and editing: Yuerong Lai and Zhimin Liu; resources: Chongjie Tong and Xin Huang; supervision: Xin Huang.

Corresponding author

Correspondence to Xin Huang.

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The authors declare that they have no conflict of interest.

Ethical approval

Ethical approval was obtained by the institutional review board of Sun Yat-sen University Cancer Center (B2018-169-01). The procedures were in accordance with the ethical standards.

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Informed consent was obtained from all patients.

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Wang, Y., Lai, Y., Peng, H. et al. Multiparametric immune profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: an exploratory study of the CLAP trial. Clin Transl Oncol 25, 256–268 (2023). https://doi.org/10.1007/s12094-022-02945-1

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  • DOI: https://doi.org/10.1007/s12094-022-02945-1

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