Circadian disruption, notably induced by light at night (LAN), is increasingly recognized as a modulator of systemic immune function; however, its high-resolution spatiotemporal impact and relevance to cancer immunotherapy remain poorly defined. Here, we constructed a spatiotemporal single-cell transcriptomic atlas of murine lymph nodes, peripheral blood, and spleen across circadian time points to dissect the immunological consequences of LAN exposure. We observed that LAN exposure was associated with profound, tissue-specific transcriptional remodeling of the adaptive immune system. Specifically, B cells exhibited suppressed circadian clock programs and impaired homing and retention signatures. Concurrently, CD8+ T cells exhibited transcriptional profiles consistent with an aberrantly activated, late-effector state, a transition accompanied by altered intercellular MHC-I communication. To evaluate the translational relevance of these transcriptomic shifts, we developed a computational LAN Immune Dyssynchrony Score (LAN-IDS) and projected these murine-derived signatures onto human cancer cohorts. In human melanoma sentinel lymph nodes, the LAN-associated CD8+ T cell trajectory exhibited strong directional concordance with advanced (Stage III) disease. Crucially, interrogating these signatures within a clinical melanoma cohort revealed that the aberrantly activated CD8+ T cell program is significantly elevated in patients with primary resistance to anti-PD-1 immunotherapy. Collectively, our cross-species computational analysis identifies a spatiotemporal adaptive immune dyssynchrony signature. These findings identify specific lymphocyte transcriptional states that may serve as candidate correlates of tumor progression and immunotherapy non-response.
