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. 2024 Nov 25;31(12):7476-7493.
doi: 10.3390/curroncol31120552.

The Potential of PD-1 and PD-L1 as Prognostic and Predictive Biomarkers in Colorectal Adenocarcinoma Based on TILs Grading

Nur Rahmah Rasyid  1   2 , Upik Anderiani Miskad  1   2 , Muhammad Husni Cangara  1   2 , Syarifuddin Wahid  1   2 , Djumadi Achmad  1   2 , Suryani Tawali  3 , Mardiati Mardiati  2
Affiliations

The Potential of PD-1 and PD-L1 as Prognostic and Predictive Biomarkers in Colorectal Adenocarcinoma Based on TILs Grading

Nur Rahmah Rasyid et al. Curr Oncol. .

Abstract

Aim: Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate. Tumor-infiltrating lymphocytes (TILs) play a crucial role in the immune response against tumors. Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are key immune checkpoints regulating T cells in the tumor microenvironment. This study aimed to assess the relationships among PD-1 expression on TILs, PD-L1 expression in tumors, and TIL grading in colorectal adenocarcinoma.

Methods: A cross-sectional design was employed to analyze 130 colorectal adenocarcinoma samples. The expression of PD-1 and PD-L1 was assessed through immunohistochemistry. A semi-quantitative scoring system was applied. Statistical analysis with the chi-square test was performed to explore correlations, with the data analyzed in SPSS version 27.

Results: PD-1 expression on TILs significantly correlated with a higher TIL grading (p < 0.001), while PD-L1 expression in tumors showed an inverse correlation with TIL grading (p < 0.001).

Conclusions: The expression of PD-1 on TILs and PD-L1 on tumor cells correlated significantly with the grading of TILs in colorectal adenocarcinoma. This finding shows potential as a predictive biomarker for PD-1/PD-L1 blockade therapy. Further studies are needed to strengthen these results.

Keywords: PD-1; PD-L1; biomarkers; colorectal cancer; immunotherapy; tumor infiltrating lymphocytes.

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Conflict of interest statement

The authors declare no competing interests. The funders were not involved in the design of the study, data collection, analysis, or interpretation, nor in the writing of the manuscript or the decision to publish the findings.

Figures

Figure 1
Figure 1
Representative images of TILs score (H.E, 200× magnification). Low-grade TILs with scores of 5% (A) and 10% (B). Intermediate-grade TILs with scores of 20% (C) and 40% (D). High-grade TILs with scores of 80% (E) and 90% (F).
Figure 2
Figure 2
Representative images of immunohistochemistry intensity staining for PD-1 on TILs. Score 0 means not stained on lymphocyte cells (A) and score 1 is faintly stained on the membrane and/or cytoplasm of lymphocyte cells (B). Score 2 means PD-1 is stained on the membrane and/or cytoplasm of lymphocyte cells with moderate intensity, i.e., yellowish color (C,D). Score 3 means PD-1 is stained wholly or partially circularly on the membrane surface and/or cytoplasm of lymphocyte cells with high intensity, i.e., a light brown color (E,F). The arrows indicate the intensity of PD-1 staining.
Figure 3
Figure 3
PD-L1 expression intensity score in the tumor cells. Score 0 means not stained in tumor cells (A) and score 1 means faintly stained in the membrane and/or cytoplasm of tumor cells (B). Score 2 means PD-L1 is stained in the membrane and/or cytoplasm of tumor cells with moderate intensity, i.e., yellowish color (C,D). Score 3 means PD-L1 is stained wholly or partially circularly on the membrane and/or cytoplasm of tumor cells with high intensity, i.e., a light brown color (E,F).
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