T Follicular Helper cell and CD8+ T Cell Dynamics in Breast Cancer: Insights from Patient Samples and Immune Checkpoint Blockade in Murine Model 2308437

Abstract

Abstract Introduction Breast cancer (BC) in India shows distinct epidemiological features, yet immune profiling remains limited. We investigated the role of T follicular helper (Tfh) cells, B-cell subsets, and CD8+ T-cell contributions to anti-tumor immunity in Indian patients and evaluated their modulation in preclinical murine models. Methods Immune cell infiltration in tumor (T) and tumor-draining lymph node (TDLN) samples from treatment-naïve BC patients was analyzed using multiparametric flow cytometry, qRT-PCR, and ELISA. To validate these observations, we utilized an orthotopic murine breast cancer model to examine the impact of immune checkpoint blockade (ICB) therapy. Results Our analysis revealed distinct alterations in Tfh cell frequency, associated with B cell activation signatures in paired BC patient samples, highlighting a potentially underexplored humoral immune axis in the Indian population. CD8+ T cells displayed heterogeneous effector states characterized by high-PD1 expression and other exhaustion markers, suggesting functional diversification of CD8+ T cells in the tumor niche. ICB therapy in a 4T1-induced TNBC mouse model markedly remodeled Tfh and CD8+ T-cell compartments, enhancing cytokine production and strengthening crosstalk with B cells in TDLNs. Although PD-1 expression has been viewed as a marker of T-cell exhaustion, emerging evidence indicates that PD-1high Tfh and CD8+ subsets can retain potent anti-tumor functions. Our study aims to determine how ICB modulates PD-1high immune cell populations–specifically whether therapy alters exhaustion versus effector states and remodels the overall tumor immune landscape. Conclusion Together, these observations indicate that coordinated Tfh—B—CD8 interactions may serve as measurable immunological biomarkers with prognostic and therapeutic relevance. Funding Source ICMR (Sanction No. EMDR/SG/15/2023-1532, dated 04.04.2024) Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)