Infiltration of CD8+ T cells in Non-Small Cell Lung Cancer is Associated with Dedifferentiation of Cancer Cells, but not with Prognosis

Abstract

CD8+ T cells infiltrating within cancer cell nests in human colorectal cancer were associated with a favorable patients' survival, suggesting the presence of anti-tumor immunity. The present study was designed to examine this concept in non-small cell lung cancer (NSCLC) by a retrospective analysis of 128 surgically resected cases. Immunohistochemical analysis showed that the number of CD8+ T cells within cancer cell nests in NSCLC was related to the histological subtype (large cell carcinoma or squamous cell carcinoma > adenocarcinoma) and the degree of dedifferentiation (undifferentiated type > differentiated type). In contrast to colorectal cancer, the number of CD8+ T cells in NSCLC had no statistically significant impact on the patients' survival. The present study demonstrated that the degree of infiltration of CD8+ T cells within cancer cell nests is dependent on the dedifferentiation of cancer cells in NSCLC, which could be one of the important aspects for the study of tumor immunity.

Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma

“…Moreover, we found that the level of CD8 þ T-cell infiltration within cancer cell nests had significant correlations with tumour dedifferentiation and histological subtype in NSCLC, consistent with previous reports (Mori et al, 2000;Wakabayashi et al, 2003). One possible reason for these results is a difference in immunogenicity of each subtype of cancer.…”

“…However, in NSCLC, the role of TILs for the survival of patients is still controversial. Consistent with the previous results (Mori et al, 2000;Wakabayashi et al, 2003), the present study demonstrated that neither CD8 þ T cells within cancer cell nests nor those in cancer stroma had a significant impact on patient survival. The reasons for this discrepancy were difficult to explain, because the antitumour effect of CD8 þ T cells may be circumvented by various mechanisms in the tumour cells.…”

“…In NSCLC, however, the relationship between patient prognosis and the presence of TILs is still obscure. The infiltration of natural killer cells or macrophages into tumours was previously found to indicate a favourable prognosis (Takeo et al, 1986;Takanami et al, 2001), whereas the presence of tumour-infiltrating CD8 þ T cells was not found to be a predictor of patient survival (Mori et al, 2000;Wakabayashi et al, 2003).…”

Density of Tumor-Infiltrating FOXP3+ T Cells as a Response Marker for Induction Chemoradiotherapy and a Potential Prognostic Factor in Patients Treated with Trimodality Therapy for Locally Advanced Non-Small Cell Lung Cancer

“…To date, reports of the prognostic impact of tumorinfiltrating CD8+ T cells in NSCLC have yielded conflicting results, i.e., positive, [22][23][24] negative, 25) and no relationship 26) with survival. The importance of localization of infiltrated CD8+ T cells, i.e., in tumor nests or tumor stroma, on clinical outcomes is still controversial.…”

Natural killer cells infiltrating human nonsmall‐cell lung cancer are enriched in CD56brightCD16− cells and display an impaired capability to kill tumor cells

“…Remarkably, in this regard the infiltration of NK cells was found to indicate a favorable prognosis, 19,20 whereas the presence of tumor-infiltrating CD8 1 T cells was not a predictor of patient survival. 24,25 However, the interpretation of these studies, as well as the development of rational NK cellbased therapeutic attempts, have been hampered by the lack of information on NK cells infiltrating NSCLC.…”