Surgical resection of pulmonary adenocarcinoma is considered to be curative but progression-free
survival (PFS) has remained highly variable. Antitumor immune response may be important,
however, the prognostic significance of tumor-infiltrating natural killer (NK) and
regulatory T (Treg) lymphocytes is uncertain. Resected pulmonary adenocarcinoma tissues
(n = 115) were studied by immunohistochemical detection of NKp46 and FoxP3 positivity
to identify NK and Treg cells, respectively. Association of cell densities with clinicopathological
features and progression-free survival (PFS) as well as overall survival (OS) were
analyzed with a follow-up time of 60 months. Both types of immune cells were accumulated
predominantly in tumor stroma. NK cell density showed association with female gender,
non-smoking and KRAS wild-type status. According to Kaplan-Meier analysis, PFS and
OS proved to be longer in patients with high NK or Treg cell densities (p = 0.0293
and p = 0.0375 for PFS, p = 0.0310 and p = 0.0448 for OS, respectively). Evaluating
the prognostic effect of the combination of NK and Treg cell density values revealed
that PFS and OS were significantly longer in NKhigh/Treghigh cases compared to the
other groups combined (p = 0.0223 and p = 0.0325, respectively). Multivariate Cox
regression analysis indicated that high NK cell density was independent predictor
of longer PFS while high NK and high Treg cell densities both proved significant predictors
of longer OS. The NKhigh/Treghigh combination also proved to be an independent prognostic
factor for both PFS and OS. In conclusion, NK and Treg cells can be components of
the innate and adaptive immune response at action against progression of pulmonary
adenocarcinoma.
