TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors

Cristina Maccalli, Samantha Scaramuzza, Giorgio Parmiani

Research output: Contribution to journalReview article

41 Citations (Scopus)

Abstract

Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses. Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore, through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs expression by tumor cells.

Original languageEnglish
Pages (from-to)801-808
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume58
Issue number5
DOIs
Publication statusPublished - May 2009
Externally publishedYes

Fingerprint

T-Lymphocytes
Neoplasms
Melanoma
Colorectal Neoplasms
Immunologic Monitoring
Adaptive Immunity
Innate Immunity
Clone Cells
Lymphocytes
Ligands

Keywords

  • Immune responses
  • NKG2D
  • TNK
  • Tumors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors. / Maccalli, Cristina; Scaramuzza, Samantha; Parmiani, Giorgio.

In: Cancer Immunology, Immunotherapy, Vol. 58, No. 5, 05.2009, p. 801-808.

Research output: Contribution to journalReview article

Maccalli, Cristina ; Scaramuzza, Samantha ; Parmiani, Giorgio. / TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors. In: Cancer Immunology, Immunotherapy. 2009 ; Vol. 58, No. 5. pp. 801-808.
@article{f28fd73c32e745e5b095d8e30ecd8f47,
title = "TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors",
abstract = "Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses. Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore, through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs expression by tumor cells.",
keywords = "Immune responses, NKG2D, TNK, Tumors",
author = "Cristina Maccalli and Samantha Scaramuzza and Giorgio Parmiani",
year = "2009",
month = "5",
doi = "10.1007/s00262-008-0635-x",
language = "English",
volume = "58",
pages = "801--808",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "5",

}

TY - JOUR

T1 - TNK cells (NKG2D+ CD8+ or CD4+ T lymphocytes) in the control of human tumors

AU - Maccalli, Cristina

AU - Scaramuzza, Samantha

AU - Parmiani, Giorgio

PY - 2009/5

Y1 - 2009/5

N2 - Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses. Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore, through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs expression by tumor cells.

AB - Innate and adaptive immune responses have many interactions that are regulated by the balance of signals initiated by a variety of activatory and inhibitory receptors. Among these, the NKG2D molecule was identified as expressed by T lymphocytes, including most CD8+ cells and a minority of CD4+ cells, designated TNK cells in this paper. Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. Aberrant expression of NKG2DLs by cancer cells, such as the release of soluble form of NKG2DLs, can lead to the impairment of these immune responses. Here, we discuss the significance of NKG2D in TNK-mediated anti-tumor activity. Our studies demonstrate that NKG2D+ T cells (TNK) are commonly recruited at the tumor site in melanoma patients where they may exert anti-tumor activity by engaging both TCR and NKG2D. Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. Notably, heterogeneous expression of NKG2DLs was found in melanoma and CRC cells, with a decrease of these molecules along with tumor progression. Therefore, through the mechanisms that govern NKG2D engagement in anti-tumor activity and the expression of NKG2DLs by tumor cells that still need to be dissected, we showed that NKG2D expressing TNK cells are a relevant T cell subtype for immunosurveillance of tumors and we propose that new immunotherapeutic interventions for cancer patients should be aimed also at enhancing NKG2DLs expression by tumor cells.

KW - Immune responses

KW - NKG2D

KW - TNK

KW - Tumors

UR - http://www.scopus.com/inward/record.url?scp=61349121360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61349121360&partnerID=8YFLogxK

U2 - 10.1007/s00262-008-0635-x

DO - 10.1007/s00262-008-0635-x

M3 - Review article

VL - 58

SP - 801

EP - 808

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 5

ER -