SERS-enabled immune monitoring: Decoding the tumor microenvironment for precision Cancer immunotherapy

The tumor immune microenvironment (TME) is pivotal in regulating cancer initiation, progression, and therapeutic response. Despite major advances in immunotherapy, clinical outcomes remain limited by low response rates and unpredictable immune-related adverse events (irAEs). Surface-enhanced Raman scattering (SERS) technology, with its single-molecule sensitivity and multiplexing capabilities, offers a transformative approach for dynamic TME profiling. This review highlights recent progress in SERS-enabled immune monitoring, including quantitative detection of immune checkpoint molecules (e.g., PD-L1, CTLA-4, TIM-3) with detection limits down to 10^-10-10^-12 M, as well as cytokine profiling (IL-6, TNF-α, IFN-γ) for early diagnosis of cytokine storms. We further discuss SERS-based identification of circulating tumor cells (CTCs) and exosomes, achieving single-particle resolution through label-free spectral fingerprints. Integrating artificial intelligence (AI) and multi-omics analysis has enabled automated classification of immune phenotypes and prediction of therapeutic outcomes with >90% accuracy in preclinical models. Finally, we address translational challenges such as signal reproducibility, clinical standardization, and cost-effectiveness and envision the future of SERS as a clinically deployable platform for precision immunotherapy and real-time immune response navigation.