0716-Discussion
0716-Discussion
In the present study, we first explored the association between pretreatment NLR and clinical outcomes in NSCLC patients receiving immunotherapy in previously published studies, and found that high pretreatment NLR values corresponded to poorer PFS and OS.
We further validated the results in our retrospective cohort.
Taken together, our results suggest that NLR may be a potential peripheral blood biomarker and an effective tool to stratify patients who are likely to benefit from ICI therapy.
Inflammation plays a key role in tumor development, affecting the survival of cancer patients (47–49).
The utility of NLR lies in its ability to reflect the degree of inflammation in a patients body (7, 14, 50), and a series of studies have confirmed its relationship with tumor prognosis (7, 51–54).
The relationship between tumor and inflammation has attracted wide attention since as early as the nineteenth century, when Rudolf Virchow discovered the presence of leukocytes in tumor tissues, and the potential relationship between tumor and inflammation was first proposed (55).
Epidemiological studies have demonstrated that ~25% of cancer cases can be attributed to infection and chronic inflammation (56).
In addition, inflammation can promote tumorigenesis by secreting growth factors or cytokines or inducing gene mutations (57, 58).
The occurrence and development of malignant tumors are affected by the tumor microenvironment (TME) and the immune system (59, 60).
Growing evidence suggests that both neutrophils and lymphocytes, components of the immune system, are involved in tumor progression and prognosis.
The presence of neutrophils in peripheral blood indicates inflammation, and lymphocytes in peripheral blood are important indicators of the immune system, the latter of which plays an indispensable role in the pathogenesis of lung cancer (59).
As a critical component of the inflammatory response, neutrophils not only target tumor cells but also indirectly act on the TME, driving or promoting tumor development (61).
On one hand, neutrophils secrete tumor growth factors, cytokines, and chemokines, including TGF-beta, VEGF, IL-6, IL-8, IL-12, and matrix metalloproteinase, which can promote angiogenesis (15, 62).
On the other hand, tumor cells release granulocyte colony-stimulating factor (G-CSF), which can increase the number of neutrophils.
Thus, a mutually reinforcing relationship exists between neutrophils and tumor cells (63).
A recent study shows that neutrophils in NSCLC act to inhibit anti-tumor immune responses by inhibiting the cytotoxic activity of immune cells, particularly activated T cells (64, 65).
Lymphocytes are a significant component of human cellular immunity and are involved in anti-tumor immune responses.
In particular, T lymphocytes are crucial to the recognition and killing of tumor cells, thereby inhibiting tumor cell proliferation and metastasis (66, 67).
Reduction in lymphocyte count reduces the anti-tumor effect of the immune system, resulting in accelerated tumor occurrence and development (67).
Lymphocyte decrease also weakens the effectiveness of ICIs, which mainly unleashes the inhibitory signal function of T lymphocytes.
Studies have demonstrated that increased lymphocyte infiltration in tumor and TME is associated with a better response to immunotherapy and prognosis in solid tumor patients (68).
TME is an important factor in cancer progression, immune escape, invasion, and distant metastasis (69).
Given the roles of neutrophils and lymphocytes in tumor growth, changes in NLR can reflect the bodys anti-tumor status (66).
Increase in NLR suggests increase in the absolute number of neutrophils and/or decrease in the absolute number of lymphocytes and, thus, decrease in the anti-tumor effect of the immune system.
These changes are associated with a poor response to immunotherapy in cancer patients. Conversely, decrease in NLR may indicate improved anti-tumor effect and good response to immunotherapy.
Emerging evidence suggests that an increased NLR is a reliable hematologic indicator of poor prognosis in NSCLC (7, 70).
Although the cut-off value of NLR in our study was different from previous studies, we found that pretreatment and dynamic change in NLR was significantly associated with prognosis of patients receiving ICI treatment.
Further studies in large scale are needed to confirm the predictive value of pretreatment NLR in advanced NSCLC patients treated with ICIs.
In conclusion, the current study demonstrates that high pretreatment and increased NLR after immunotherapy are associated with poor outcomes of advanced NSCLC patients with ICI treatment.
Our results suggest that pretreatment NLR ≥ 6.0 and NLR increase ≥3.0 after ICI treatment are associated with significant poor PFS and OS.
NLR is a promising biomarker of the prognosis of advanced NSCLC patients receiving ICIs, which warrants further prospective studies.
Data Availability Statement
The datasets generated for this study are available on request to the corresponding author.
Ethics Statement
The study protocol was approved by the Ethics Committee of Chinese PLA general hospital. The patients/participants provided their written informed consent to participate in this study.
Author Contributions
JW and SJ conceived the idea of this article. XY, QS, GW, and RC completed the work of acquisition of data. YL and ZZ shared the task of analysis, interpretation of data, and manuscript writing. All authors participated in discussing and revising the manuscript.
Conflict of Interest
GW is an employee of 3D Medicines.
The remaining 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.
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