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. 2025 Aug 12:15:1495722.
doi: 10.3389/fonc.2025.1495722. eCollection 2025.

Expression of immune checkpoints (IDO and PD-L1) in oral tongue cancer patients: a 10-year retrospective cohort study in Pakistan

Merium Fatima  1   2 , Shaarif Bashir  3 , Syed Atif Raza  2 , Alamgeer  2 , Muhammad Hassan  4 , Muhammad Abu Bakar  5 , Ali Zafar Sheikh  6 , Muhammad Tahseen  3 , Umer Nisar Sheikh  3 , Asif Loya  3 , Muhammad Faisal  7 , Asim Farooq  4 , Kashif Asghar  4
Affiliations

Expression of immune checkpoints (IDO and PD-L1) in oral tongue cancer patients: a 10-year retrospective cohort study in Pakistan

Merium Fatima et al. Front Oncol. .

Abstract

Background: Tongue squamous cell carcinoma (TSCC) is a significant global health issue with high incidence and mortality rates. Current treatments involve surgery, radiotherapy, and chemotherapy; however, prognosis remains poor. Recent research highlights the crucial role of the tumor microenvironment, especially immune cells and checkpoints like PD-L1 and IDO, in TSCC progression.

Aim: This study aims to investigate the expression of IDO and PD-L1 in TSCC patients before and after chemotherapy and their association with patients' clinicopathological characteristics.

Materials and methods: This study involved 106 TSCC patients from Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Pakistan, with biopsies obtained from 2012 to 2022. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded (FFPE) tumor samples to evaluate IDO and PD-L1 expression before and after chemotherapy. Data on patient demographics, tumor characteristics, and treatment were collected, and follow-up continued until January 2024.

Results: The cohort had a mean age of 48.9 years, with a predominance of male patients. Prior to chemotherapy, 83% of patients were IDO-negative, and 75.5% were PD-L1-negative. Post-chemotherapy, IDO expression increased to 24.5% of patients (n = 26), with 84.6% exhibiting low expression and 15.4% showing high expression. While PD-L1 expression was increased to 29.2% (n = 31), with 90.3% of the positive cases showing low expression and 9.7% high expression. IDO expression was notably higher in multifocal tumors and correlated with increased comorbidities post-chemotherapy. Despite changes in marker expression, there was no significant difference in survival rates associated with IDO or PD-L1 expression.

Conclusion: Chemotherapy appears to upregulate IDO and PD-L1 expressions in TSCC, highlighting the potential for integrating immunotherapy into treatment regimens. Further studies are needed to explore the dynamics of these biomarkers over time and their impact on patient outcomes, emphasizing the need for comprehensive therapeutic strategies.

Keywords: IDO; PD-L1; biomarkers; chemotherapy; immunohistochemistry; immunotherapy; tongue squamous cell carcinoma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression of IDO before and after chemotherapy in the same patient, detected by immunohistochemical staining. Representative images of immunohistochemical staining for IDO in TSCC cases. (A, B) Positive IDO expression in tumor cells pre-chemotherapy; negative IDO expression post-chemotherapy. (C, D) Negative IDO expression pre-chemotherapy; positive IDO expression post-chemotherapy.
Figure 2
Figure 2
Expression of PD-L1 before and after chemotherapy in the same patient, detected by immunohistochemical staining. (A, B) Positive PD-L1 expression pre-chemotherapy; negative PD-L1 expression post-chemotherapy, (C, D) Negative PD-L1 expression pre-chemotherapy; positive PD-L1 expression post-chemotherapy.
Figure 3
Figure 3
Expression of IDO and PD-L1 in the same patient, detected by immunohistochemical staining. (A, B) IDO positive expression; PD-L1 positive expression. (C, D) IDO positive expression; PD-L1 negative expression, (E, F) IDO negative expression; PD-L1 positive expression. All images were captured at 40X magnification.
Figure 4
Figure 4
Overall survival: The five-year disease-free survival rate was 49%, with a median duration of 53 months.
See this image and copyright information in PMC

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