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. 2024 May 9;13(10):2793.
doi: 10.3390/jcm13102793.

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer

Jolanta Smok-Kalwat  1 , Paulina Mertowska  2 , Sebastian Mertowski  2 , Stanisław Góźdź  1   3 , Izabela Korona-Głowniak  4 , Wojciech Kwaśniewski  5 , Ewelina Grywalska  2
Affiliations

Analysis of Selected Toll-like Receptors in the Pathogenesis and Advancement of Non-Small-Cell Lung Cancer

Jolanta Smok-Kalwat et al. J Clin Med. .

Abstract

(1) Background: Non-small-cell lung cancer (NSCLC) represents a significant global health challenge, contributing to numerous cancer deaths. Despite advances in diagnostics and therapy, identifying reliable biomarkers for prognosis and therapeutic stratification remains difficult. Toll-like receptors (TLRs), crucial for innate immunity, now show potential as contributors to cancer development and progression. This study aims to investigate the role of TLR expression as potential biomarkers in the development and progression of NSCLC. (2) Materials and Methods: The study was conducted on 89 patients diagnosed with NSCLC and 40 healthy volunteers, for whom the prevalence of TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was assessed on selected subpopulations of T and B lymphocytes in the peripheral blood of recruited patients along with the assessment of their serum concentration. (3) Result: Our study showed several significant changes in NSCLC patients at the beginning of the study. This resulted in a 5-year follow-up of changes in selected TLRs in recruited patients. Due to the high mortality rate of NSCLC patients, only 16 patients survived the 5 years. (4) Conclusions: The results suggest that TLRs may constitute real biomarker molecules that may be used for future prognostic purposes in NSCLC. However, further validation through prospective clinical and functional studies is necessary to confirm their clinical utility. These conclusions may lead to better risk stratification and tailored interventions, benefiting NSCLC patients and bringing medicine closer to precision.

Keywords: biomarkers; clinicopathological characteristics; innate immune system; non-small-cell lung cancer; toll-like receptors; tumor progression.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the study’s design or collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Description of the role of some TLRs in the context of lung cancer (based on [10,11,12,13,14,15,16,17,18,19,20,21]).
Figure 2
Figure 2
Exemplary analysis of the cells’ immunophenotype and the determination of the percentage of positive TLR expression on the example of TLRCD4+CD3+ subpopulation marked in blue, CD8+CD3+ subpopulation in red, and CD19+CD3− subpopulation in green. Points (A–C) indicate the method of reading TLR2 using the FMO control.
Figure 3
Figure 3
Characteristics of patients with NSCLC included in the study. (A) Stages of NSCLC patients; (B) Gender of NSCLC patients; (C) Most common symptoms reported by NSCLC patients.
Figure 4
Figure 4
Graphical representation of the results regarding the evaluation of the percentage of TLR2- and TLR3-positive peripheral blood lymphocyte populations tested. (A) Percentage of CD4+TLR2+ lymphocytes; (B) Percentage of CD8+TLR2+ lymphocytes; (C) Percentage of CD19+TLR2+ lymphocytes; (D) Percentage of CD4+TLR3+ lymphocytes; (E) Percentage of CD8+TLR3+ lymphocytes; (F) Percentage of CD19+TLR3+ lymphocytes; * Statistically significant results are marked.
Figure 5
Figure 5
Graphical representation of the results regarding the evaluation of the percentage of TLR4- and TLR7-positive peripheral blood lymphocyte populations tested. (A) Percentage of CD4+TLR4+ lymphocytes; (B) Percentage of CD8+TLR4+ lymphocytes; (C) Percentage of CD19+TLR4+ lymphocytes; (D) Percentage of CD4+TLR7+ lymphocytes; (E) Percentage of CD8+TLR7+ lymphocytes; (F) Percentage of CD19+TLR7+ lymphocytes; * Statistically significant results are marked.
Figure 6
Figure 6
Graphical representation of the results regarding the evaluation of the percentage of TLR8- and TLR9-positive peripheral blood lymphocyte populations tested. (A) Percentage of CD4+TLR8+ lymphocytes; (B) Percentage of CD8+TLR8+ lymphocytes; (C) Percentage of CD19+TLR8+ lymphocytes; (D) Percentage of CD4+TLR9+ lymphocytes; (E) Percentage of CD8+TLR9+ lymphocytes; (F) Percentage of CD19+TLR9+ lymphocytes; * Statistically significant results are marked.
Figure 7
Figure 7
Graphical representation of Spearman rank correlations obtained for NSCLC dead (A) and NSCLC alive (B) patients. Positive correlations are marked in blue, while negative correlations are marked in red. The differentiation of shades of the mentioned colors is equivalent to the level of correlation. By positive correlations, we mean that as one parameter increases, the values of the other parameter increase, while by negative correlations we mean that as the value of one parameter increases, the values of the other parameter decrease. Abbreviations: CD—cluster of differentiation; TLR—Toll-like receptors; sTLR—soluble form of Toll-like receptors.
Figure 8
Figure 8
Graphical representation of the ROC analysis of selected immunophenotype parameters of dead NSCLC and alive NSCLC patients: (A) ROC curve for TLR2-positive lymphocyte percentage; (B) ROC curve for the percentage of TLR3-positive lymphocytes; (C) ROC curve for the percentage of TLR4-positive lymphocytes; (D) ROC curve for the percentage of TLR7-positive lymphocytes; (E) ROC curve for the percentage of TLR8-positive lymphocytes; (F) ROC curve for the percentage of TLR9-positive lymphocytes. Abbreviations: CD—cluster of differentiation; TLR—Toll-like receptors; ROC—Receiver Operating Characteristic.
Figure 9
Figure 9
Graphical representation of ROC analysis of dissolved TLR concentrations for dead NSCLC and alive NSCLC patients: (A) ROC curve for sTLR2; (B) ROC curve for sTLR3; (C) ROC curve for sTLR4; (D) ROC curve for sTLR7; (E) ROC curve for sTLR8; (F) ROC curve for sTLR9. Abbreviations: sTLR—soluble form of Toll-like receptors; ROC—Receiver Operating Characteristic.
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