Current concepts of tumor-infiltrating lymphocytes in human malignancies

Shin Heng Chiou, Bor Ching Sheu, Wen Chun Chang, Su Cheng Huang, Ho Hong-Nerng

Research output: Contribution to journalShort survey

68 Citations (Scopus)

Abstract

Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs were literally defined as "tumor-infiltrating lymphocytes", which a posteriori locate within the tumor tissues. Although such cells can be found, they fail to control the growth of tumor. Many have proposed diverse mechanisms for dysfunction of TILs with regard to the roles of immunosurveillance against cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits brought by activating these cells for immunotherapy. Functional defects of TILs have been linked to abnormalities of signaling molecules; however, there is conflicting data. The death of TILs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TILs and animal models, the compromise of tumor-specific immune responses was thought to result from not only mechanisms of clonal anergy but also exhaustion and/or deletion. Furthermore, functional cytotoxic CD8 + TILs might be rendered incompetent by cancer-induced up-regulation of inhibitory NK receptors or proximal signaling abnormalities. Additionally, immune privilege was partly attributed to recruitment of regulatory T cells to the tumor sites. The failure of IL-2 signaling, which stands at the center of T cell functionalities, had been linked to the enzymatic activity of cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO expression, an important enzyme in pregnancy-related immunosuppression, by cancer cells might play a role in tumor immunity. The disparity of cancer types, origin, developmental stages and individual genetic backgrounds likely account for differences, or even contradictions, which might be the reason why immunotherapy works only on a few cancer types. Delineating the mechanisms behind functional defects of TILs can help not only boost chances of the development of a successful cure but understand the not fully identified roles played by immune system in the face of malignancies.

Original languageEnglish
Pages (from-to)35-50
Number of pages16
JournalJournal of Reproductive Immunology
Volume67
Issue number1-2
DOIs
Publication statusPublished - Jan 1 2005
Externally publishedYes

Fingerprint

Tumor-Infiltrating Lymphocytes
Pregnancy
Neoplasms
Immunotherapy
Immune System
Clonal Anergy
Immunologic Monitoring
Regulatory T-Lymphocytes
Matrix Metalloproteinases

Keywords

  • Human malignancies
  • Pregnancy
  • Tumor immunology
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynaecology

Cite this

Current concepts of tumor-infiltrating lymphocytes in human malignancies. / Chiou, Shin Heng; Sheu, Bor Ching; Chang, Wen Chun; Huang, Su Cheng; Hong-Nerng, Ho.

In: Journal of Reproductive Immunology, Vol. 67, No. 1-2, 01.01.2005, p. 35-50.

Research output: Contribution to journalShort survey

Chiou, Shin Heng ; Sheu, Bor Ching ; Chang, Wen Chun ; Huang, Su Cheng ; Hong-Nerng, Ho. / Current concepts of tumor-infiltrating lymphocytes in human malignancies. In: Journal of Reproductive Immunology. 2005 ; Vol. 67, No. 1-2. pp. 35-50.
@article{eb5fb3f53a874233af832d786768497d,
title = "Current concepts of tumor-infiltrating lymphocytes in human malignancies",
abstract = "Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs were literally defined as {"}tumor-infiltrating lymphocytes{"}, which a posteriori locate within the tumor tissues. Although such cells can be found, they fail to control the growth of tumor. Many have proposed diverse mechanisms for dysfunction of TILs with regard to the roles of immunosurveillance against cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits brought by activating these cells for immunotherapy. Functional defects of TILs have been linked to abnormalities of signaling molecules; however, there is conflicting data. The death of TILs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TILs and animal models, the compromise of tumor-specific immune responses was thought to result from not only mechanisms of clonal anergy but also exhaustion and/or deletion. Furthermore, functional cytotoxic CD8 + TILs might be rendered incompetent by cancer-induced up-regulation of inhibitory NK receptors or proximal signaling abnormalities. Additionally, immune privilege was partly attributed to recruitment of regulatory T cells to the tumor sites. The failure of IL-2 signaling, which stands at the center of T cell functionalities, had been linked to the enzymatic activity of cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO expression, an important enzyme in pregnancy-related immunosuppression, by cancer cells might play a role in tumor immunity. The disparity of cancer types, origin, developmental stages and individual genetic backgrounds likely account for differences, or even contradictions, which might be the reason why immunotherapy works only on a few cancer types. Delineating the mechanisms behind functional defects of TILs can help not only boost chances of the development of a successful cure but understand the not fully identified roles played by immune system in the face of malignancies.",
keywords = "Human malignancies, Pregnancy, Tumor immunology, Tumor-infiltrating lymphocytes",
author = "Chiou, {Shin Heng} and Sheu, {Bor Ching} and Chang, {Wen Chun} and Huang, {Su Cheng} and Ho Hong-Nerng",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.jri.2005.06.002",
language = "English",
volume = "67",
pages = "35--50",
journal = "Journal of Reproductive Immunology",
issn = "0165-0378",
publisher = "Elsevier Ireland Ltd",
number = "1-2",

}

TY - JOUR

T1 - Current concepts of tumor-infiltrating lymphocytes in human malignancies

AU - Chiou, Shin Heng

AU - Sheu, Bor Ching

AU - Chang, Wen Chun

AU - Huang, Su Cheng

AU - Hong-Nerng, Ho

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs were literally defined as "tumor-infiltrating lymphocytes", which a posteriori locate within the tumor tissues. Although such cells can be found, they fail to control the growth of tumor. Many have proposed diverse mechanisms for dysfunction of TILs with regard to the roles of immunosurveillance against cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits brought by activating these cells for immunotherapy. Functional defects of TILs have been linked to abnormalities of signaling molecules; however, there is conflicting data. The death of TILs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TILs and animal models, the compromise of tumor-specific immune responses was thought to result from not only mechanisms of clonal anergy but also exhaustion and/or deletion. Furthermore, functional cytotoxic CD8 + TILs might be rendered incompetent by cancer-induced up-regulation of inhibitory NK receptors or proximal signaling abnormalities. Additionally, immune privilege was partly attributed to recruitment of regulatory T cells to the tumor sites. The failure of IL-2 signaling, which stands at the center of T cell functionalities, had been linked to the enzymatic activity of cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO expression, an important enzyme in pregnancy-related immunosuppression, by cancer cells might play a role in tumor immunity. The disparity of cancer types, origin, developmental stages and individual genetic backgrounds likely account for differences, or even contradictions, which might be the reason why immunotherapy works only on a few cancer types. Delineating the mechanisms behind functional defects of TILs can help not only boost chances of the development of a successful cure but understand the not fully identified roles played by immune system in the face of malignancies.

AB - Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs were literally defined as "tumor-infiltrating lymphocytes", which a posteriori locate within the tumor tissues. Although such cells can be found, they fail to control the growth of tumor. Many have proposed diverse mechanisms for dysfunction of TILs with regard to the roles of immunosurveillance against cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits brought by activating these cells for immunotherapy. Functional defects of TILs have been linked to abnormalities of signaling molecules; however, there is conflicting data. The death of TILs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TILs and animal models, the compromise of tumor-specific immune responses was thought to result from not only mechanisms of clonal anergy but also exhaustion and/or deletion. Furthermore, functional cytotoxic CD8 + TILs might be rendered incompetent by cancer-induced up-regulation of inhibitory NK receptors or proximal signaling abnormalities. Additionally, immune privilege was partly attributed to recruitment of regulatory T cells to the tumor sites. The failure of IL-2 signaling, which stands at the center of T cell functionalities, had been linked to the enzymatic activity of cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO expression, an important enzyme in pregnancy-related immunosuppression, by cancer cells might play a role in tumor immunity. The disparity of cancer types, origin, developmental stages and individual genetic backgrounds likely account for differences, or even contradictions, which might be the reason why immunotherapy works only on a few cancer types. Delineating the mechanisms behind functional defects of TILs can help not only boost chances of the development of a successful cure but understand the not fully identified roles played by immune system in the face of malignancies.

KW - Human malignancies

KW - Pregnancy

KW - Tumor immunology

KW - Tumor-infiltrating lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=26244441316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=26244441316&partnerID=8YFLogxK

U2 - 10.1016/j.jri.2005.06.002

DO - 10.1016/j.jri.2005.06.002

M3 - Short survey

C2 - 16111767

AN - SCOPUS:26244441316

VL - 67

SP - 35

EP - 50

JO - Journal of Reproductive Immunology

JF - Journal of Reproductive Immunology

SN - 0165-0378

IS - 1-2

ER -