Tumor immune microenvironment in cancer patients with leukocytosis

Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRL^pos) and without TRL (TRL^neg) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRL^pos and TRL^neg tumors. The immunological profiles of patients in the TCGA database with high (LS^high) or low LS scores were compared. TRL^pos tumors were transcriptionally distinct from TRL^neg tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (n = 303), patients with high LS had inferior survival rates compared to those with low LS (P = 0.023). LS^high tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LS^high tumors also expressed higher levels of CXCR2 chemokines, CSF2, and CSF3. In the pan-cancer cohort (n = 9984), LS^high tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.