title: Subtypes of cytotoxic lymphocytes and natural killer cells infiltrating cancer nests correlate with prognosis in patients with vulvar squamous cell carcinoma.
abstract: OBJECTIVE
  Adaptive immune effectors do not influence prognosis in vulvar squamous cell carcinoma (vSCC). Therefore, we tried to clarify the prognostic role of innate immunity and granzyme B-dependent cytotoxicity as defined by intratumoral infiltrates of natural killer cells (CD56+) and lymphocytes expressing granzyme B (GrB+).
  
  
  METHODS
  We analyzed 76 primary vSCCs and 35 lymph node metastases that were obtained from 76 patients with a full clinical history. The distribution and density of GrB+ and CD56+ cells within cancer tissues were evaluated by immunohistochemistry and correlated with clinicopathological features, commonly recognized prognostic factors and overall survival (OS).
  
  
  RESULTS
  CD56+ cells were mostly detected within the cancer nests, while GrB+ cells were predominant in the tumor stroma. Intraepithelial (IE) CD56+ infiltrates at the primary site were correlated with depth of invasion (r = 0.339, p = 0.003) and recurrence (r = 0.295, p = 0.011), while IE GrB+ infiltrates were correlated with tumor grade (r = 0.304, p = 0.009) and age (r = 0.333, p = 0.004). The primary cancer nests of metastatic patients were infiltrated more by intraepithelial (IE) CD56+ cells than were those of the non-metastatic patients (p = 0.05). The median OS was 41.16 months (range 1.7-98.43). High IE GrB+ infiltrates predicted longer OS among patients without metastases (p = 0.028). High IE CD56+ infiltrates were correlated with longer OS in metastatic cases (p = 0.009).
  
  
  CONCLUSIONS
  The combined cytotoxicity of innate and adaptive immune effectors infiltrating cancer nests (IE GrB+) predicts an improved clinical outcome among non-metastatic vSCC patients. The functional status of prognostic IE CD56+ infiltrates in immune escaped (metastatic) tumors requires further investigation.
authors.affiliation: Department of Oncological Surgery, The Medical University of Gdańsk, ul. Smoluchowskiego 17, 80-214, Gdańsk, Poland, jacek.sznurkowski@gumed.edu.pl.
authors.forename: Jacek Jan
authors.initials: JJ
authors.lastname: Sznurkowski
authors.forename: Anton
authors.initials: A
authors.lastname: Zawrocki
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019002:CD56 Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D008207:Lymphatic Metastasis; D016131:Lymphocyte Subsets / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014846:Vulvar Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality
chemical_list: D019002:CD56 Antigen; D053804:Granzymes