A cohort study finds that class-switched B cells could potentially be used as a prognostic marker for non-small cell lung cancer and as a target for future therapeutic strategies.

Lung cancer is a major global health concern. Significant progress has been made in treatment, with immunotherapy emerging as a recent breakthrough of great promise. The most promising immunotherapy approach utilizes antibodies to prevent inhibition of T cells in the immune system, enabling their anti-cancer activity. Antibodies that target programmed death receptor (PD)-1, programmed death-ligand (PD-L)1, and cytotoxic T-lymphocyte-associated protein 4 receptor (CTLA-4) have shown remarkable effectiveness in prolonging the lives of certain patients. 

While the role of T cells in lung cancer is widely acknowledged, there has been comparatively less research on B cells. B cells are present in lung tumors, but their quantity varies depending on the stage and histological subtype. This study, published in the American Journal of Cancer Research, used flow cytometry to analyze subpopulations of peripheral T and B cells and explored their prognostic significance in patients with non-small cell lung cancer (NSCLC).

Study Participants

A total of 60 lung cancer patients were included in the study, with 31 classified as early-stage and 29 categorized as advanced-stage. Adenocarcinoma emerged as the most prevalent cancer type across both stages. Early-stage patients primarliy underwent surgical resection, while all advanced-stage patients received systemic therapy options such as immunotherapy, targeted therapy, or chemotherapy.

Immune Cell Subsets in Cancer Patients Compared to Controls

The study compared the B and T cell populations of cancer patients with those of healthy controls. Cancer patients displayed a lower frequency of marginal B cells (IgD+CD27+) and CD32+ B cells (p = 0.020 and p = 0.016, respectively) compared to controls.

In terms of T cells, advanced-stage patients had higher levels of effector memory CD8+ T cells and lower levels of naïve CD8+ T cells. Additionally, they displayed a reduced frequency of CD27+CD28+CD4+ T cells and an increased frequency of CD28-CD28-CD8+ T cells. Notably, there was no significant difference in PD-1 expression on T cells between the stages.

Advanced-stage patients showed significantly higher levels of various inflammatory cytokines (IL-1B, IL-4, IL-6, IL-8, etc.) compared to early-stage patients (p values ranged from 0.001 to 0.09).

Immune Cell Subsets in Early vs. Advanced Stages

The study further analyzed variations in immune cell populations between early and advanced stages of lung cancer. Linear regression analysis showed a significant correlation between advanced-stage disease and frequencies of memory B cells, class-switched B cells, class-switched memory B cells, and plasmablasts compared to early-stage patients (p values ranged from 0.012 to 0.039) compared to early-stage patients (p values ranged from 0.001 to 0.09).

Class-Switched B Cells and Survival in Lung Cancer

Survival analysis was conducted on the advanced-stage patient group. A higher frequency of class-switched B cells emerged as a significant indicator of worse prognosis (HR: 3.054, 95% CI: 1.007–9.262, p = 0.049). While not statistically significant, some T cell subtypes and cytokine levels suggested potential prognostic value, warranting further investigation. Multivariate analysis confirmed a higher proportion of class-switched B cells as an independent risk factor for poorer survival (HR: 2.272, 95% CI: 1.339–6.897, p = 0.044).

Class-Switched B Cells: Prognostic Marker and Therapeutic Target

Analysis revealed a significant correlation between the frequency of class-switched B cells and various T cell subtypes, suggesting a potential interaction between these immune cell populations. Class-switched B cells could be a potential prognostic marker and a target for future therapeutic strategies.

Source:

Lee, I. (2024). Synergistic B and T lymphocyte interaction: prognostic implications in non-small cell lung cancer. American Journal of Cancer Research, 14(3), 1227–1242. https://doi.org/10.62347/tdiv2436 

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