• Good review article of current theories on cancer and immunity.
• Underscores the importance of the functional competence of the cells involved,
all of which are impacted by either immune aging and/or severe depletion.
Annu Rev Immunol. 2011 Apr 23;29:235-71.
Natural innate and adaptive immunity to cancer.
Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ.
Department of Pathology and Immunology, Washington University School of Medicine, Missouri, USA.
Abstract - The immune system can identify and destroy nascent tumor cells in a process
termed cancer immunosurveillance, which functions as an important defense against cancer.
Recently, data obtained from numerous investigations in mouse models of cancer and in
humans with cancer offer compelling evidence that particular innate and adaptive immune
cell types, effector molecules, and pathways can sometimes collectively function as extrinsic
tumor-suppressor mechanisms. However, the immune system can also promote tumor
progression. Together, the dual host-protective and tumor-promoting actions of immunity
are referred to as cancer immunoediting. In this review, we discuss the current experimental
and human clinical data supporting a cancer immunoediting process that provide the
fundamental basis for further study of immunity to cancer and for the rational design of
immunotherapies against cancer.
• Discusses importance and complexity of roles that CD4 T cells play in anti-tumor response.
CD4 cells are one of the lymphocyte subsets known to be significantly affected (functional
competence, as well as diversity) by both aging and immunodepletion.
• This review also highlights the vast array of subtypes of CD4 and CD8 T cells. Very little is
known about the relative distribution of these within the body or the potential effects on
particular subtypes as a consequence of repeated depletion of these cells from the circulation.
Immunol Rev. 2008 Apr;222:129-44.
Multiple roles for CD4+ T cells in anti-tumor immune responses.
Kennedy R, Celis E.
Mayo Vaccine Research Group, Mayo Clinic College of Medicine, Rochester, MN, USA.
Abstract - Our understanding of the importance of CD4+ T cells in orchestrating immune responses has
grown dramatically over the past decade. This lymphocyte family consists of diverse subsets ranging from
interferon-gamma (IFN-gamma)-producing T-helper 1 (Th1) cells to transforming growth factor-beta (TGF-
beta)-secreting T-regulatory cells, which have opposite roles in modulating immune responses to
pathogens, tumor cells, and self-antigens. This review briefly addresses the various T-cell subsets within
the CD4+ T-cell family and discusses recent research efforts aimed at elucidating the nature of the 'T-cell
help' that has been shown to be essential for optimal immune function. Particular attention is paid to the
role of Th cells in tumor immunotherapy. We review some of our own work in the field describing how
CD4+ Th cells can enhance anti-tumor cytotoxic T-lymphocyte (CTL) responses by enhancing clonal
expansion at the tumor site, preventing activation-induced cell death and functioning as antigen-
presenting cells for CTLs to preferentially generate immune memory cells. These unconventional roles for
Th lymphocytes, which require direct cell-to-cell communication with CTLs, are clear examples of how
versatile these immunoregulatory cells are.
• If a key way that tumors escape the immune system in the first place is by
antigenic drift, this underscores the paramount importance of naïve T cells in the
ongoing battle against this ever-changing tumor. As can be seen in the papers on
immune aging and the consequences of lymphodepletion, naïve T cell functional
capacity, as well as diversity of naïve T cell repertoire is significantly impacted by
both of these.
J Clin Invest. 2003 May;111(10):1487-96.
Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T
Bai XF, Liu J, Li O, Zheng P, Liu Y.
Division of Cancer Immunology, Department of Pathology, Ohio State University
Medical Center, USA.
Abstract - It is established that mutations in viral antigenic epitopes, or antigenic
drifts, allow viruses to escape recognition by both Ab's and T lymphocytes. It is
unclear, however, whether tumor cells can escape immune recognition via antigenic
drift. Here we show that adoptive therapy with both monoclonal and polyclonal
transgenic CTLs, specific for a natural tumor antigen, P1A, selects for multiple
mutations in the P1A antigenic epitope. These mutations severely diminish T cell
recognition of the tumor antigen by a variety of mechanisms, including modulation of
MHC:peptide interaction and TCR binding to MHC:peptide complex. These results
provide the first evidence for tumor evasion of T cell recognition by antigenic drift,
and thus have important implications for the strategy of tumor immunotherapy.
Free Full Text : http://www.jci.org/articles/view/17656
• Evidence for a crucial contribution of NK cells to tumor immunosurveillance. NK
cells are also known to be affected by aging, though less is known about specific
consequences of immunodepletion on this specialized subset of lymphocytes.
Oncogene. 2008 Oct 6;27(45):5932-43.
NK cells and cancer immunosurveillance.
Waldhauer I, Steinle A.
Department of Immunology, Eberhard Karls University of Tübingen, Tübingen,
Natural killer (NK) cells are lymphocytes of the innate immune system that monitor
cell surfaces of autologous cells for an aberrant expression of MHC class I molecules
and cell stress markers. Since their first description more than 30 years ago, NK cells
have been implicated in the immune defence against tumours. Here, we review the
broadly accumulating evidence for a crucial contribution of NK cells to the
immunosurveillance of tumours and the molecular mechanisms that allow NK cells to
distinguish malignant from healthy cells. Particular emphasis is placed on the
activating NK receptor NKG2D, which recognizes a variety of MHC class I-related
molecules believed to act as 'immuno-alerters' on malignant cells, and on tumour-
mediated counterstrategies promoting escape from NKG2D-mediated recognition.