Expression of CD94/NKG2 subtypes on tumor-infiltrating lymphocytes in primary and metastatic melanoma
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Updated: Aug 10, 2026
Evaluation of Tumor-infiltrating Leukocyte Subsets in a Subcutaneous Tumor Model
Published on: April 13, 2015
C S Vetter1, P T Straten, P Terheyden
1Department of Dermatology, University of Würzburg, Germany.
Abstract:
Natural killer receptors are expressed both on natural killer populations and subpopulations of T cells, mainly alpha/beta TCR+CD8+ T cells. We have characterized the expression of the C-type lectin natural killer receptor CD94/NKG2 on tumor-infiltrating lymphocytes in primary and metastatic melanoma lesions. By immunohistochemistry, 5-10% of the tumor-infiltrating lymphocytes, both in primary and metastatic lesions, expressed CD94. More than 95% of these CD94+ cells coexpressed CD8 and the percentage of CD94 expression within the CD8+ cell population ranged from 5 to 20% with a higher expression in metastatic lesions. CD94/NKG2 exists both in an inhibitory and an activating form; thus, it was necessary to determine whether the inhibitory CD94/NKG2-A/B, the activating CD94/NKG2-C/E, or both were expressed on tumor-infiltrating lymphocytes. Reverse transcription-polymerase chain reaction using specific primers for NKG2-A/B and C/E mRNA revealed the presence of NKG2-C/E in all primary and metastatic lesions. In contrast, the inhibitory NKG2-A/B was only present in 50% of primary tumors whereas 80% of tumor-infiltrating lymphocytes in metastatic lesions expressed these transcripts. In healthy humans, the mean number of inhibitory natural killer receptors is higher than that of activating receptors, but the opposite was true for tumor-infiltrating lymphocytes in melanoma. The reversal of the ratio of inhibitory to activating natural killer receptors among tumor-infiltrating lymphocytes suggests a regulated event due to either specific factors within the tumor microenvironment, preferential homing of T cell subsets, or certain stages of T cell activation.
Insights
Natural killer receptor CD94/NKG2 is expressed on melanoma tumor-infiltrating lymphocytes. The ratio of activating to inhibitory receptors is reversed in these cells compared to healthy individuals, suggesting a tumor microenvironment influence.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Natural killer (NK) receptors, including CD94/NKG2, are present on NK cells and T cell subpopulations.
- These receptors play roles in immune surveillance and can exist in inhibitory or activating forms.
Purpose of the Study:
- To characterize the expression of CD94/NKG2 on tumor-infiltrating lymphocytes (TILs) in melanoma.
- To determine the balance between inhibitory (NKG2-A/B) and activating (NKG2-C/E) forms of CD94/NKG2 on TILs.
Main Methods:
- Immunohistochemistry was used to detect CD94 expression on TILs in primary and metastatic melanoma lesions.
- Reverse transcription-polymerase chain reaction (RT-PCR) was employed to analyze the expression of NKG2-A/B and NKG2-C/E mRNA.
Main Results:
- CD94 was expressed on 5-10% of TILs in both primary and metastatic melanoma, predominantly on CD8+ T cells (over 95%).
- Activating NKG2-C/E transcripts were found in all lesions, while inhibitory NKG2-A/B transcripts were less frequent in primary tumors (50%) but more prevalent in metastatic lesions (80%).
- The ratio of activating to inhibitory NK receptors on TILs was reversed compared to healthy individuals.
Conclusions:
- TILs in melanoma exhibit a distinct expression pattern of CD94/NKG2, with a higher proportion of activating receptors.
- This altered receptor balance may be a regulated event influenced by the tumor microenvironment, T cell homing, or activation status.
