Impact of Chemotherapy on Circulating Lymphocyte Subsets in Lung Cancer Patients

Abstract

Purpose: Lung cancer remains a leading cause of cancer-related death and chemotherapy stands as a fundamental component in therapy. Chemotherapy-induced myelosuppression encompasses a spectrum of hematological declines, including not only neutrophils but also lymphocytes, hemoglobin levels and platelets. This retrospective cohort study investigates alterations in peripheral blood lymphocyte subsets. By uncovering these changes, our goal is to refine patient management strategies, ensuring that the benefits of chemotherapy are maximized while minimizing its detrimental effects.

Patients and methods: We retrospectively analyzed 159 lung cancer patients. Patients were categorized as "NT" (n=108, no previous anti-tumor therapy), and "PT" (n=51, prior therapy followed by at least a two-month treatment-free interval). Post-chemotherapy, patients were reassessed and grouped into "EarlyCycle" for those who underwent four or fewer cycles, and "LateCycle" for those who underwent more than four cycles.

Results: The study focused on analyzing the percentages of lymphocyte subsets, including T cells (CD4+, CD8+), B cells, and natural killer (NK) cells, across these groups. For T cells, the EarlyCycle group exhibited a significant increase compared to NT (0.7783 vs 0.7271; p=0.0017) and PT (0.7783 vs 0.6804; p=1.6e-05). B cells showed a significant decrease from NT to LateCycle (0.1014 vs 0.0817; p=2.2e-05) and from PT to LateCycle (0.1317 vs 0.0817; p=6.2e-10). NK cells significantly decreased in the EarlyCycle group compared to NT (0.1109 vs 0.1462; p=0.00816) and PT (0.1109 vs 0.1513; p=0.00992), with no significant change in the LateCycle group compared to either NT or PT (p>0.05).

Conclusion: Chemotherapy significantly affects lymphocyte subsets in a treatment-specific manner. The EarlyCycle group experienced a reduction in NK cell and an increase in T cell, suggesting a damage of innate immunity and an early shift towards adaptive immunity. The LateCycle group showed a substantial decrease in B cell, indicating a delayed effect on humoral immunity components.

Keywords: chemotherapy; lung cancer; lymphocyte subsets; myelosuppression; peripheral blood.

Figure 1

Flow Cytometry. (a) Scatter plot showing CD45 PerCP-H versus SSC-H. The cells in cycle are CD45 strong positive and SSC low. (b) Scatter plot illustrating CD3 FITC-H versus SSC-H. The left part is CD3- and and SSC low. The right part is CD3+ and and SSC low. (c) Scatter plot of CD4 APC-H versus CD8 PE-H, displaying the distribution within CD3+ T cells. The Q1 part is CD3+ and CD8+ cytotoxic T cells. The Q3 part is CD3+ and CD4+ helper T cells. (d) Scatter plot of CD19 APC-H versus CD16+56+ PE-H, indicating the distribution of B cells (CD19+) and NK cells (CD16+56+) within CD3- cells. The Q1 part is CD3- and CD16+56+ NK cells. The Q3 part is CD3- and CD19+ B cells.

Figure 2

Median and Mean percentages of T cells (including CD4+ T cells and CD8+ T cells). (a) Bar chart of Median and Mean percentages of T cells. (b) Heatmap of median percentages of T cells show changes between each group. (c) Bar chart of Median and Mean percentages of CD4+ T cells. (d) Heatmap of median percentages of CD4+ T cells show changes between each group. (e) Bar chart of Median and Mean percentages of CD8+ T cells. There are no significant changes between each group of CD8+ T cells, so there is no heatmap of CD8+ T cells. In the bar charts, the Orange is mean and the green is median. In the heatmaps, the dark blue represents a significant change between the two groups and the light blue and red represent no significant changes between the two groups.

Figure 3

Median and Mean percentages of B cells. (a) Bar chart of Median and Mean percentages of B cells. (b) Heatmap of median percentages of B cells show changes between each group.

Figure 4

Median and Mean percentages of NK cells. (a) Bar chart of Median and Mean percentages of NK cells. (b) Heatmap of median percentages of NK cells show changes between each group.