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

Lien Lippens (UGent) , Mieke Van Bockstal (UGent) , Emiel De Jaeghere (UGent) , Philippe Tummers (UGent) , Amin Makar (UGent) , Sofie De Geyter (UGent) , Koen Van de Vijver (UGent) , An Hendrix (UGent) , Katrien Vandecasteele (UGent) and Hannelore Denys (UGent)
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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
Cancer Research, Oncology

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MLA
Lippens, Lien, et al. “Immunologic Impact of Chemoradiation in Cervical Cancer and How Immune Cell Infiltration Could Lead towards Personalized Treatment.” International Journal of Cancer, Wiley, 2020.
APA
Lippens, L., Van Bockstal, M., De Jaeghere, E., Tummers, P., Makar, A., De Geyter, S., … Denys, H. (2020). Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead towards personalized treatment. International Journal of Cancer.
Chicago author-date
Lippens, Lien, Mieke Van Bockstal, Emiel De Jaeghere, Philippe Tummers, Amin Makar, Sofie De Geyter, Koen Van de Vijver, An Hendrix, Katrien Vandecasteele, and Hannelore Denys. 2020. “Immunologic Impact of Chemoradiation in Cervical Cancer and How Immune Cell Infiltration Could Lead towards Personalized Treatment.” International Journal of Cancer.
Chicago author-date (all authors)
Lippens, Lien, Mieke Van Bockstal, Emiel De Jaeghere, Philippe Tummers, Amin Makar, Sofie De Geyter, Koen Van de Vijver, An Hendrix, Katrien Vandecasteele, and Hannelore Denys. 2020. “Immunologic Impact of Chemoradiation in Cervical Cancer and How Immune Cell Infiltration Could Lead towards Personalized Treatment.” International Journal of Cancer.
Vancouver
1.
Lippens L, Van Bockstal M, De Jaeghere E, Tummers P, Makar A, De Geyter S, et al. Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead towards personalized treatment. International Journal of Cancer. 2020;
IEEE
[1]
L. Lippens et al., “Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead towards personalized treatment,” International Journal of Cancer, 2020.
@article{8647709,
  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.},
  author       = {Lippens, Lien and Van Bockstal, Mieke and De Jaeghere, Emiel and Tummers, Philippe and Makar, Amin and De Geyter, Sofie and Van de Vijver, Koen and Hendrix, An and Vandecasteele, Katrien and Denys, Hannelore},
  issn         = {0020-7136},
  journal      = {International Journal of Cancer},
  keywords     = {Cancer Research,Oncology},
  language     = {eng},
  publisher    = {Wiley},
  title        = {Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead towards personalized treatment},
  url          = {http://dx.doi.org/10.1002/ijc.32893},
  year         = {2020},
}

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