Increased Intratumor Vα24-Positive Natural Killer T Cells: A Prognostic Factor for Primary Colorectal Carcinomas

Abstract

Purpose: Human invariant natural killer T (NKT) cells are novel, distinct lymphocyte populations with a restricted T-cell receptor repertoire (Va24-Vh11). They play a pivotal role in immunoregulation and in antitumor activities. This study focused on Va24 + NKT cells in colorectal carcinomas and their clinicopathologic significance. Experimental Design: Va24 + NKT-cell infiltration immunohistochemistry was studied in a total of 103 colorectal carcinoma cases. The degree of NKT-cell infiltration in tumors was evaluated as low (<7 NKTcells/5 HPF) or high (z7 NKT cells/5 HPF). The correlation between the degree of infiltrated Va24 + NKTcells and clinicopathologic variables was studied statistically. Results: A small number of Va24 + NKT cells were found in the normal colorectal mucosa (2.6 F 3.7 cells/5 HPF); however, their number increased remarkably in colorectal carcinomas (15.2 F 16.3 cells/5 HPF; P = 0.0003) and a majority showed phenotype of activation. Higher NKT-cell infiltration was more frequent in women than in men (P = 0.034) and correlated with fewer lymph node metastases (P = 0.042). Patients with high NKT-cell infiltration showed higher overall (P = 0.018) as well as disease-free (P = 0.0006) survival rates. Intratumor NKT-cell infiltration was an independent prognostic factor for the overall (P = 0.033) and disease-free (P = 0.0064) survival rates. Conclusions: Increased infiltration of Va24+ NKT cells was observed in colorectal carcinomas. HigherVa24 + NKT-cell infiltration in colorectal carcinomas was an independent prognostic factor for favorable prognosis.

Effects of the Administration of High-Dose Interleukin-2 on Immunoregulatory Cell Subsets in Patients with Advanced Melanoma and Renal Cell Cancer

“…6, 7). Importantly, the circulating pool of iNKT cells shows quantitative and qualitative defects in cancer patients (8,9), which seem to be clinically relevant, as increased numbers of intratumoral or circulating iNKT cells are associated with improved prognosis (10,11). 4 In contrast to iNKT cells, CD4 +…”

A Phase I-II Study of α-Galactosylceramide-Pulsed IL-2/GM-CSF-Cultured Peripheral Blood Mononuclear Cells in Patients with Advanced and Recurrent Non-Small Cell Lung Cancer

“…In the surgically resected specimens of lung cancer or colorectal cancer, the frequency of intratumor V␣24 NKT cells increased significantly (20), and the accumulation of V␣24 NKT cells in the region of colorectal cancer was related to a better survival (20,45). Thus, a study focusing on the immunological analyses of the tumor site, including the assessment of NKT cell-dependent antitumor reactions at molecular levels would be of interest.…”

Vγ9Vδ2-T cells as antigen presenting cells for iNKT cell based cancer immunotherapy

“…Furthermore, deficient iNKT numbers predict poor clinical outcome in various tumor types, including colon carcinoma, neuroblastoma, and head and neck squamous cell carcinoma. [3][4][5] iNKT can be activated by the synthetic glycolipid ligand a-galactosylceramide (a-GalCer) presented by CD1d-expressing antigen presenting cells (APC) and various strategies to exploit the antitumor characteristics of iNKT have been employed in immunotherapy clinical trials for advanced cancer. In a Phase I trial, intravenous (i.v.)…”