Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment

Int J Cancer. 2020 Jul 15;147(2):554-564. doi: 10.1002/ijc.32893. Epub 2020 Feb 26.

Abstract

We investigated the potential of tumor-infiltrating immune cells (ICs) as predictive or prognostic biomarkers for cervical cancer patients. In total, 38 patients treated with (chemo)radiotherapy and subsequent surgery were included in the current study. This unique treatment schedule makes it possible to analyze IC markers in pretreatment and posttreatment tissue specimens and their changes during treatment. IC markers for T cells (CD3, CD4, CD8 and FoxP3), macrophages (CD68 and CD163) and B cells (CD20), as well as IL33 and PD-L1, were retrospectively analyzed via immunohistochemistry. Patients were grouped in the low score or high score group based on the amount of positive cells on immunohistochemistry. Correlations to pathological complete response (pCR), cause-specific survival (CSS) and metastasis development during follow-up were evaluated. In analysis of pretreatment biopsies, significantly more pCR was seen for patients with CD8 = CD3, CD8 ≥ CD4, positive IL33 tumor cell (TC) scores, IL33 IC < TC and PD-L1 TC ≥5%. Besides patients with high CD8 scores, also patients with CD8 ≥ CD4, CD163 ≥ CD68 or PD-L1 IC ≥5% had better CSS. In the analysis of posttreatment specimens, less pCR was observed for patients with high CD8 or CD163 scores. Patients with decreasing CD8 or CD163 scores between pretreatment and posttreatment samples showed more pCR, whereas those with increasing CD8 or decreasing IL33 IC scores showed a worse CSS. Meanwhile, patients with an increasing CD3 score or stable/increasing PD-L1 IC score showed more metastasis during follow-up. In this way, the intratumoral IC landscape is a promising tool for prediction of outcome and response to (chemo)radiotherapy.

Keywords: biomarker; cervical cancer; chemoradiation; immunologic response; tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / immunology
  • B7-H1 Antigen / metabolism*
  • CD3 Complex / metabolism*
  • Chemoradiotherapy / methods*
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Macrophages / immunology
  • Middle Aged
  • Precision Medicine
  • Prognosis
  • Retrospective Studies
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Tumor Microenvironment
  • Urogenital Surgical Procedures
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CD3 Complex