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000182606 1001_ $$0P:(DE-He78)80e100a16534f5fc67f7436ee67a47f9$$aRühle, Alexander$$b0$$eFirst author
000182606 245__ $$aPrognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy.
000182606 260__ $$aLondon$$bBioMed Central$$c2022
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000182606 520__ $$aTumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population.Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses.While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels.LAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC.
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000182606 650_7 $$2Other$$aElderly
000182606 650_7 $$2Other$$aGeriatric
000182606 650_7 $$2Other$$aHead-and-neck cancer
000182606 650_7 $$2Other$$aImmune checkpoint
000182606 650_7 $$2Other$$aImmunosenescence
000182606 650_7 $$2Other$$aRadiotherapy
000182606 650_7 $$2Other$$aTumor-infiltrating lymphocytes
000182606 7001_ $$aTodorovic, Jovan$$b1
000182606 7001_ $$0P:(DE-HGF)0$$aSpohn, Simon S K$$b2
000182606 7001_ $$0P:(DE-HGF)0$$aGkika, Eleni$$b3
000182606 7001_ $$aBecker, Christoph$$b4
000182606 7001_ $$aKnopf, Andreas$$b5
000182606 7001_ $$0P:(DE-HGF)0$$aZamboglou, Constantinos$$b6
000182606 7001_ $$0P:(DE-HGF)0$$aSprave, Tanja$$b7
000182606 7001_ $$aWerner, Martin$$b8
000182606 7001_ $$0P:(DE-HGF)0$$aGrosu, Anca-Ligia$$b9
000182606 7001_ $$aKayser, Gian$$b10
000182606 7001_ $$0P:(DE-He78)8d52e7ff1ccaac7dbf0232fdcb0168bd$$aNicolay, Nils$$b11$$eLast author
000182606 773__ $$0PERI:(DE-600)2224965-5$$a10.1186/s13014-022-02153-9$$gVol. 17, no. 1, p. 181$$n1$$p181$$tRadiation oncology$$v17$$x1748-717X$$y2022
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