By integrating bedside function (HLA-DR trajectories, LPS-induced cytokine capacity) with single-cell endotypes (MS1/HLA-DR^low S100A^high monocytes, dendritic-cell attrition, checkpoint-biased T cells) and host–pathogen topology from FFPE-ready spatial assays, emerging strategies aim to restore antigen presentation, reconstitute priming, disrupt inhibitory myeloid–lymphoid circuits and prevent secondary infection. The gene discussed is S100A1; the disease is infection.