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Original research
Intraepithelial tumor-infiltrating lymphocytes shape loco-regional PET/CT spread of locally advanced cervical cancer
  1. Mathilde Del1,
  2. Claire Illac2,
  3. Mathilde Morisseau3,
  4. Martina Aida Angeles1,
  5. Anne Ducassou4,
  6. Sarah Betrian5,
  7. Guillaume Bataillon6,
  8. Gwenael Ferron1,7,
  9. Elodie Chantalat8,
  10. Erwan Gabiache9 and
  11. Alejandra Martinez1,10
    1. 1 Department of Surgical Oncology, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France
    2. 2 Department of Pathology, Institut Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France
    3. 3 Department of Biostatistics, Institut Claudius Regaud, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France
    4. 4 Radiation Oncology and Brachytherapy Department, Institut Universitaire du Cancer de Toulouse - Oncopole, Institut Claudius Regaud, Toulouse, France
    5. 5 Department of Medical Oncology, Institut Universitaire du Cancer de Toulouse, Toulouse, France
    6. 6 Department of Anatomopathology, Toulouse University Cancer Institute, Toulouse, France
    7. 7 Team 19, ONCOSARC - Oncogenesis of Sarcomas, Cancer Research Center of Toulouse (CRCT) - INSERM UMR 1037, Toulouse, France
    8. 8 Department of Surgical Oncology, University Hospital Centre Toulouse IUC Oncopole CHU Division, Toulouse, France
    9. 9 Department of Nuclear Medicine, Cancer University Institute Toulouse Oncopole, Toulouse, France
    10. 10 Team 1, Tumor Immunology and Immunotherapy, Cancer Research Center of Toulouse (CRCT) - INSERM UMR 1037, Toulouse, France
    1. Correspondence to Dr Mathilde Del, Institute Claudius Regaud, Toulouse, France; mathilde.del{at}hotmail.com

    Abstract

    Background Data suggest an association between positron emission tomography/CT (PET/CT) metabolic metrics and tumor microenvironment in several malignancies, and a potential role of PET/CT to monitor response to immunotherapy.

    Objective To evaluate the correlation between tumor loco-regional extension and tumor-infiltrating lymphocyte infiltration in locally advanced cervical cancer prior to concurrent chemo-radiotherapy.

    The secondary objective was to assess the association between tumor-infiltrating lymphocytes and PET/CT metabolic metrics.

    Methods Patients with locally advanced cervical cancer and negative para-aortic extensions on PET/CT were included. Two senior nuclear medicine physicians specializing in gynecologic oncology reviewed all PET/CT exams, and extracted tumor maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis, as well as pelvic lymph node involvement. One senior gynecologic oncology pathologist assessed intraepithelial tumor-infiltrating lymphocytes and stromal tumor-infiltrating lymphocytes. Intraepithelial tumor-infiltrating lymphocytes were categorized following previous studies as <1% and >1%. The cut-off for stromal tumor-infiltrating lymphocytes was chosen empirically: intermediate <60% and high >60%.

    Results 86 patients were included. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with tumor metabolic metrics. Intraepithelial tumor-infiltrating lymphocytes were not significantly associated with maximum standard uptake value (p=0.16), or metabolic tumor volume (p=0.19). Tumors with <1% intraepithelial tumor-infiltrating lymphocytes score were associated with a higher MRI tumor size (≥ median) (63.3% vs 39.3%, p=0.04). Patients with pelvic lymph node uptake were significantly more frequent in patients with high stromal tumor-infiltrating lymphocytes score (≥60%) (61.5% vs 31.7%, p=0.009).

    Conclusions Poor or absent intraepithelial tumor-infiltrating lymphocytes were associated with more advanced disease at diagnosis and larger tumor size. Tumor-infiltrating lymphocytes were not associated with tumor metabolic activity. Intraepithelial and stroma tumor-infiltrating lymphocytes are not redundant and should be assessed separately. Further work is needed to evaluate the association between tumor metabolic profile and immune populations, including different T-cell subtypes for patient selection for immunotherapy strategies.

    • cervical cancer
    • lymph nodes

    Data availability statement

    Data are available upon reasonable request.

    https://doi.org/10.1136/ijgc-2023-004677

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      Data availability statement

      Data are available upon reasonable request.

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      Footnotes

      • Twitter @MathildeDel2, @AngelesFite, @Alejandra

      • Contributors MD: guarantorconceptualization, data curation, methodology, writing – original draft. CI: conceptualization, data curation, methodology, statistical analyses, writing – original draft. MA, AD, SB: data curation, methodology, writing – original draft. GB, GF, EC, EG, MM, AM: conceptualization, project administration, methodology, writing – review. MD and AM accept responsibility for the overall content/data.

      • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

      • Competing interests None declared.

      • Provenance and peer review Not commissioned; externally peer reviewed.

      • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.