Postdoctoral Fellow University of Calcutta Kolkata, West Bengal, India
Disclosure(s):
Poulomi Khamaru, PhD: No financial relationships to disclose
Introduction/Rationale: 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.
