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Evaluation of PD-L1 Expression and Systemic Inflammatory Blood Cell Ratios as Prognosticators in Advanced Lung, Breast and Head and Neck Cancers
by
, , , ,
Taoufik Nedjadi
1,*
,
Sultanah AlBoraie
2,
Wardah Alghamdi
2,
Raghad Alkharouby
2,
Lama Almuraee
2,
Dalal Malibari
1,
Alaa Samkari
1,3,
Samera Alosairi
3,
Rawiah Alsiary
1,
Mohamed Bilal Nedjadi
4,
Majed Ramadan
1 and
Mohamed Eldigire Ahmed
5 1
King Abdullah International Medical Research Centre, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Jeddah 21423, Saudi Arabia
2
Department of Medicine, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia
3
Department of Pathology and Laboratory Medicine, Ministry of National Guard-Health Affairs, Jeddah 22384, Saudi Arabia
4
Department of Medicine, University College London, London WC1E 6BT, UK
5
College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Jeddah 21423, Saudi Arabia
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(11), 1819; https://doi.org/10.3390/cancers18111819
Submission received: 14 April 2026
/
Revised: 24 May 2026
/
Accepted: 27 May 2026
/
Published: 1 June 2026
(This article belongs to the Section Cancer Biomarkers)
Simple Summary
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionised the landscape of cancer treatment. PD-L1 is an established biomarker used to guide immunotherapy decisions in several types of cancer. However, its value in predicting patient survival remains inconsistent and may vary between cancer types. In this study, we evaluated PD-L1 expression in patients with advanced lung, breast, and head and neck cancers and examined its relationship with clinicopathological features, overall survival and systemic inflammatory blood markers. Although PD-L1 expression was common across the three cancer groups, it was not significantly associated with overall survival in any of them. In contrast, the platelet-to-lymphocyte ratio, a simple blood-based inflammatory marker, showed a significant association with PD-L1 expression in lung cancer and emerged as an important prognosticator, particularly in lung and breast cancers. Complementary bioinformatics analysis revealed that PD-L1 is linked to immunoregulatory gene network and positively correlated with CD8+ T cell, neutrophil and dendritic cell infiltration across all three cancer types. Collectively, these findings highlight the limited standalone prognostic utility of PD-L1 in advanced solid tumours and suggest that integrating tumour biomarkers with systemic inflammatory markers may offer a more comprehensive and clinically useful approach for predicting outcomes in patients with advanced cancers.
Abstract
Introduction: Immunotherapy with immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has become an established treatment strategy across various malignancies. In this context, PD-L1 expression plays a key role in the clinical management of cancer patients. However, the prognostic significance of PD-L1 expression remains inconsistent across different cancer types. This study aimed to evaluate the prevalence of PD-L1 expression in three cancer types and to examine its association with key clinicopathological parameters, systemic inflammatory markers and patient outcomes. Methods: A retrospective cohort of 141 patients with lung, breast and head and neck cancers diagnosed between 2016 and 2021 was analysed. PD-L1 expression was analysed by immunohistochemistry using clone 22C3 and the scoring system for positivity was determined according to standard clinical scoring practices for each tumour type. Systemic inflammatory markers, including the platelet-to-lymphocyte ratio (PLR), were calculated from pre-treatment blood counts. Correlation and survival analyses were performed to evaluate the associations between PD-L1 expression levels, clinicopathological characteristics and prognosis. Bioinformatics analyses using GeneMania, STRING and TIMER (v.3) databases were conducted to explore functional enrichment, protein–protein interactions and immune-cell infiltration associated with PD-L1 expression. Results: PD-L1 positivity (≥1%) was observed in 56.75% of lung cancer cases, 44% of breast cancer cases and 92.85% of head and neck cancer cases. PD-L1 expression alone was not significantly associated with overall survival across the cancer cohorts. However, it was significantly associated with PLR in the lung cancer cohort (p = 0.036). Notably, low PLR was associated with improved survival in both lung cancer (p = 0.007) and breast cancer (p = 0.031). Bioinformatics analysis identified several PD-L1-interacting genes, including PD-1, CTLA4 and PTPN and demonstrated strong positive correlations between PD-L1 expression and the infiltration of CD8+ T cells, neutrophils and dendritic cells across the analysed malignancies. Conclusions: Despite its high expression in advanced solid tumours, PD-L1 showed limited prognostic value in our cancer cohort. In contrast, systemic inflammatory markers particularly PLR, emerged as a potential indicator of clinical outcome. Our data suggest that integrating PD-L1 status with systemic inflammatory markers may improve outcome prediction and help inform therapeutic decision-making in patients with advanced malignancies.
