What question did this study set out to answer?

This study aims to investigate the relationship between plasma immunoglobulin levels and clinical outcomes in advanced non-small cell lung cancer patients receiving anti-PD-1 therapy.

April 23, 2026Scientific Reports0 citationsOpen Access

Elevated plasma IgG is associated with improved treatment response and survival in advanced non‑small cell lung cancer patients treated with anti‑PD‑1 therapy

RORyotaro Ohkuma NONobuyuki Onishi MWMakoto Watanabe

Puntos clave

This study aims to investigate the relationship between plasma immunoglobulin levels and clinical outcomes in advanced non-small cell lung cancer patients receiving anti-PD-1 therapy.
Conducted a single-center retrospective analysis of 55 NSCLC patients treated with anti-PD-1-based regimens.
Measured plasma IgG, IgA, and IgM levels at baseline and after 1–4 treatment cycles.
Evaluated associations with objective response, progression-free survival (PFS), and overall survival (OS).
In anti-PD-1 monotherapy, higher post-treatment IgG levels were linked to better PFS and OS.
IgG levels decreased significantly in the chemotherapy plus anti-PD-1 group but showed no significant change in monotherapy.
Multivariable analysis revealed higher post-treatment IgG as an independent predictor of better survival outcomes.

Resumen

Immune checkpoint inhibitors (ICIs) targeting PD-1 improve outcomes in advanced non-small cell lung cancer (NSCLC), but responses are heterogeneous and tissue biomarkers are imperfect. Circulating immunoglobulins integrate B- and T-cell function and may reflect systemic immune competence. We investigated whether plasma immunoglobulin levels during ICI therapy are associated with clinical outcomes in stage IV NSCLC. In this single-center retrospective study, 55 patients received anti-PD-1-based regimens: anti-PD-1 monotherapy (n = 31), chemotherapy plus anti-PD-1 (n = 18), or ipilimumab plus nivolumab (n = 6). Plasma IgG, IgA, and IgM were measured at baseline and after 1–4 cycles, and associations with objective response, progression-free survival (PFS), and overall survival (OS) were evaluated. In the chemotherapy plus anti-PD-1 group, IgG decreased significantly on treatment (p = 0.0030), whereas no significant changes in any isotype were observed with anti-PD-1 monotherapy. In the monotherapy cohort, post-treatment IgG was higher in responders than in non-responders (p = 0.0262) and was associated with longer PFS (p = 0.0218) and OS (p = 0.0166). In multivariable Cox models in the monotherapy cohort, higher post-treatment IgG remained independently associated with longer PFS (adjusted HR 0.28, 95% CI 0.11–0.75; p = 0.011) and OS (adjusted HR 0.29, 95% CI 0.09–0.87; p = 0.028). Sensitivity analyses incorporating PD-L1 status and 6-week landmark analyses showed similar trends. In exploratory pooled analyses, no significant association between post-treatment IgG and PFS or OS was observed across all 55 patients. IgA and IgM were not significantly associated with outcomes. Higher early on-treatment plasma IgG may serve as a non-invasive biomarker of favorable outcome, particularly in the anti-PD-1 monotherapy setting, warranting prospective validation and mechanistic studies.

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