title: [Expression levels of co-inhibitory molecules CTLA-4, LAG-3, PD-1 and CD39 on CD4⁺ T cells correlate with progression of non-small cell lung cancer].
abstract: OBJECTIVE
  To detect the expression levels of co-inhibitory molecules, including CTLA-4, LAG-3, PD-1 and CD39, on CD4⁺ T cells in peripheral blood or tumor tissues from NSCLC patients and to investigate their potential internal relationships with the progression of NSCLC.
  
  
  METHODS
  Eighty-eight patients including 53 NSCLC, 17 disease control cases and 18 healthy controls were studied. All the peripheral blood and 13 cases of tumor and tumor-adjacent tissues from surgically treated NSCLC patients were obtained. The expression levels of co-inhibitory molecules CTLA-4, LAG-3, PD-1 and CD39 were assayed by flow cytometry (FCM).
  
  
  RESULTS
  The ratios of CD4⁺ CTLA-4⁺ T cells, CD4⁺ LAG-3⁺ T cells, CD4⁺ PD-1⁺ T cells and CD4⁺ CD39⁺ T cells in the peripheral blood of NSCLC patients were (2.49 ± 2.43)%, (2.47 ± 3.50)%, (12.94 ± 5.96)% and (6.78 ± 5.21)%, respectively, the ratio of CD4⁺ CTLA-4⁺ T cells was significantly higher in the peripheral blood of NSCLC patients than that in the disease controls and healthy controls (P < 0.05) . The ratio of CD4(+)PD-1⁺ T cells was also highly raised in the peripheral blood of NSCLC patients than that in the healthy controls (P < 0.05). Further stratified analysis indicated that the ratio of CD4⁺ PD-1⁺ T cells was (13.21 ± 5.96)% in NSCLC patients entering stages III and IV, also significantly increased as compared with that of (11.06 ± 3.42)% in the patients undergoing stages I and II (P < 0.05). More CD4⁺ CTLA-4⁺ T cells, CD4⁺ LAG-3⁺ T cells and CD4⁺ PD-1⁺ T cells were verified in the cancer tissues (5.07 ± 2.11)%, (7.86 ± 3.24)% and (40.20 ± 18.84)%, respectively, than those in their matched peripheral blood (3.13 ± 1.01)%, (2.65 ± 1.48)% and (15.79 ± 5.69)%, (P < 0.05 for all), and especially, CD4⁺ CTLA-4⁺ T cells and CD4⁺ PD-1⁺ T cells were also highly increased than those in matched cancer-adjacent tissues (P < 0.05 for all).
  
  
  CONCLUSIONS
  The increased expression levels of co-inhibitory molecules CTLA-4, LAG-3 and PD-1 on CD4⁺ T cells in peripheral blood and tumor tissues may be one of the mechanisms related to immune escape of tumor cells, acceleration of disease progression and poor prognosis in NSCLC patients.
authors.affiliation: Department of Laboratory Diagnosis, Changhai Hospital, the Second Military Medical University, Shanghai 200433, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wu
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.forename: Longkun
authors.initials: L
authors.lastname: Lu
authors.affiliation: Email: msminli@hotmail.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D060908:CTLA-4 Antigen / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism*; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D001081:Apyrase; C067869:CD39 antigen