Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer—Analyses of CD68, CD163, TGF-β1, GLUT-1 and HIF-1α Expressions

Weber M, Ries J, Braun K, Wehrhan F, Distel L, Geppert CI, Lutz R, Kesting MR, Trumet L (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Cells MDPI

Book Volume: 13

Article Number: 397

Journal Issue: 5

DOI: 10.3390/cells13050397

Abstract

Background: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials. In this context, the addition of radio- and chemotherapy is being reconsidered. Therefore, a better understanding of the tumor-biologic effects of neoadjuvant RCT would be beneficial. The current study was conducted on a retrospective cohort of patients who received neoadjuvant RCT for the treatment of oral cancer. The aim of the study was to evaluate the influence of neoadjuvant RCT on the immunological tumor microenvironment (TME) and hypoxic and glucose metabolisms. Methods: A cohort of 45 OSSC tissue samples from patients were analyzed before and after RCT (total 50.4 Gy; 1.8 Gy 5× weekly; Cisplatin + 5-Fluorouracil). Immunohistochemistry for CD68, CD163, TGF-β, GLUT-1 and HIF-1α was performed using tissue microarrays and automated cell counting. Differences in expression before and after RCT and associations with histomorphological parameters (T-status, N-status) were assessed using the Mann–Whitney U test. Results: Tumor resection specimens after neoadjuvant RCT showed a significant decrease in CD68 infiltration and a significant increase in CD163 cell density. The CD68/CD163 ratio was significantly lower after RCT, indicating a shift toward M2 polarization. The GLUT-1 and HIF-1α expressions were significantly lower after RCT. Larger tumors (T3/T4) showed a lower GLUT-1 expression. Other biomarkers were not associated with the T- and N-status. Conclusions: Neoadjuvant RCT with 50.4 Gy induced a shift toward the M2 polarization of macrophages in the TME. This change in immune composition is not favorable and may be prognostically negative and counteract immunotherapeutic approaches. In addition, the decreased expressions in GLUT-1 and HIF-1α indicate reductions in the glucose metabolism and hypoxic energy metabolism in response to “high dose” neoadjuvant RCT, which may be therapeutically desirable.

Authors with CRIS profile

Manuel Weber Department of Oral and Cranio-Maxillofacial Surgery Jutta Ries Department of Oral and Cranio-Maxillofacial Surgery Kristina Braun Department of Oral and Cranio-Maxillofacial Surgery Falk Wehrhan Department of Oral and Cranio-Maxillofacial Surgery Luitpold Distel Department of Radiation Oncology Carol-Immanuel Geppert Institute of Pathology Rainer Lutz Department of Oral and Cranio-Maxillofacial Surgery Marco Rainer Kesting Lehrstuhl für Zahnmedizin, insbesondere Mund-, Kiefer-, und Gesichtschirurgie Leah Trumet Department of Oral and Cranio-Maxillofacial Surgery

How to cite

APA:

Weber, M., Ries, J., Braun, K., Wehrhan, F., Distel, L., Geppert, C.-I.,... Trumet, L. (2024). Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer—Analyses of CD68, CD163, TGF-β1, GLUT-1 and HIF-1α Expressions. Cells, 13(5). https://dx.doi.org/10.3390/cells13050397

MLA:

Weber, Manuel, et al. "Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer—Analyses of CD68, CD163, TGF-β1, GLUT-1 and HIF-1α Expressions." Cells 13.5 (2024).

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