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Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy

1
1st Department of Radiology, Radiation Oncology Unit, Aretaieion University Hospital, 15772 Athens, Greece
2
Department of Pathology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
3
Department of Radiotherapy/Oncology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Curr. Oncol. 2022, 29(6), 4274-4284; https://doi.org/10.3390/curroncol29060342
Received: 18 May 2022 / Revised: 11 June 2022 / Accepted: 12 June 2022 / Published: 15 June 2022
(This article belongs to the Topic Cancer Biology and Radiation Therapy)
Microenvironmental conditions control the entrance and thriving of cytotoxic lymphocytes in tumors, allowing or preventing immune-mediated cancer cell death. We investigated the role of tumor-infiltrating lymphocyte (TIL) density in the outcome of radiotherapy in a series of squamous cell head–neck tumors (HNSCC). Moreover, we assessed the link between markers of hypoxia and TIL density. One-hundred twenty-one patients with HNSCC treated prospectively with radical radiotherapy/chemo-radiotherapy were analyzed. The assessment of TIL density was performed on hematoxylin and eosin biopsy sections before radiotherapy. TIL density ranged from 0.8 to 150 lymphocytes per ×40 optical field (median 27.5). Using the median value, patients were grouped into two categories of low and high TIL density. Early T-stage tumors had a significantly higher TIL density (p < 0.003), but we found no association with N-stage. Overexpression of HIF1α, HIF2α, and CA9 was significantly linked with poor infiltration by TILs (p < 0.03). A significant association of high TIL density with better disease-specific overall survival and improved locoregional relapse-free survival was noted (p = 0.008 and 0.02, respectively), which was also confirmed in multivariate analysis. It is concluded that HNSCC phenotypes that allow for the intratumoral accumulation of lymphocytes have a better outcome following radical radiotherapy/chemo-radiotherapy. Intratumoral-activated HIF- and CA9-related pathways characterize immunologically cold tumors and may be used as targets for therapeutic interventions. View Full-Text
Keywords: squamous cell head–neck cancer; radiotherapy; tumor-infiltrating lymphocytes; hypoxia; prognosis squamous cell head–neck cancer; radiotherapy; tumor-infiltrating lymphocytes; hypoxia; prognosis
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MDPI and ACS Style

Koukourakis, I.M.; Gkegka, A.G.; Xanthopoulou, E.; Nanos, C.; Giatromanolaki, A.; Koukourakis, M.I. Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy. Curr. Oncol. 2022, 29, 4274-4284. https://doi.org/10.3390/curroncol29060342

AMA Style

Koukourakis IM, Gkegka AG, Xanthopoulou E, Nanos C, Giatromanolaki A, Koukourakis MI. Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy. Current Oncology. 2022; 29(6):4274-4284. https://doi.org/10.3390/curroncol29060342

Chicago/Turabian Style

Koukourakis, Ioannis M., Anastasia G. Gkegka, Erasmia Xanthopoulou, Christos Nanos, Alexandra Giatromanolaki, and Michael I. Koukourakis. 2022. "Prognostic and Predictive Relevance of Tumor-Infiltrating Lymphocytes in Squamous Cell Head–Neck Cancer Patients Treated with Radical Radiotherapy/Chemo-Radiotherapy" Current Oncology 29, no. 6: 4274-4284. https://doi.org/10.3390/curroncol29060342

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