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Tumor Immune Microenvironment in Cancer Patients With Leukocytosis

 Kyung Hwan Kim  ;  Nam Suk Sim  ;  Jee Suk Chang  ;  Yong Bae Kim 
 CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol.69(7) : 1265-1277, 2020-07 
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Adult ; Aged ; Biomarkers, Tumor / genetics* ; Cohort Studies ; Female ; Follow-Up Studies ; Granulocyte-Macrophage Colony-Stimulating Factor / genetics ; Humans ; Leukocytosis / etiology* ; Leukocytosis / metabolism ; Leukocytosis / pathology ; Lymphocytes, Tumor-Infiltrating / immunology* ; Macrophages / immunology* ; Male ; Middle Aged ; Neoplasms / complications* ; Prognosis ; Receptors, Interleukin-8B / genetics ; Survival Rate ; Transcriptome* ; Tumor Microenvironment / immunology*
CXCR2 ; Gene signatures ; Leukocytosis ; Tumor immune evasion ; Tumor microenvironment
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 (TRLpos) and without TRL (TRLneg) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRLpos and TRLneg tumors. The immunological profiles of patients in the TCGA database with high (LShigh) or low LS scores were compared. TRLpos tumors were transcriptionally distinct from TRLneg 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). LShigh 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. LShigh tumors also expressed higher levels of CXCR2 chemokines, CSF2, and CSF3. In the pan-cancer cohort (n = 9984), LShigh 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.
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1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Kim, Yong Bae(김용배) ORCID logo https://orcid.org/0000-0001-7573-6862
Chang, Jee Suk(장지석) ORCID logo https://orcid.org/0000-0001-7685-3382
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