The tumour microenvironment is an important aspect of cancer biology that contributes to tumour initiation, tumour progression and responses to therapy. Cells and molecules of the immune system are a fundamental component of the tumour microenvironment.
Importantly, therapeutic strategies can harness the immune system to specifically target tumour cells and this is particularly appealing owing to the possibility of inducing tumour-specific immunological memory, which might cause long-lasting regression and prevent relapse in cancer patients.
The composition and characteristics of the tumour microenvironment vary widely and are important in determining the anti-tumour immune response. For example, certain cells of the immune system, including natural killer cells, dendritic cells (DCs) and effector T cells, are capable of driving potent anti-tumour responses.
However, tumour cells often induce an immunosuppressive microenvironment, which favours the development of immunosuppressive populations of immune cells, such as myeloid-derived suppressor cells and regulatory T cells.
Understanding the complexity of immunomodulation by tumours is important for the development of immunotherapy. Various strategies are being developed to enhance anti-tumour immune responses, including DC-based vaccines and antagonists of inhibitory signalling pathways to overcome 'immune checkpoints'. Existing therapies are also being investigated for their ability to induce an anti-tumour immune response, which could lead to the administration of combination immunotherapies that provide a more efficacious and enduring response.
However, there are issues that remain to be understood. In particular, it is clear that there is variability in the ability of a tumour to induce an immune response and hence there is debate about the determinants of tumour immunogenicity. It will be important to resolve these issues in order to predict or modulate responses to immunotherapies.
The articles in this specially commissioned Focus on Tumour immunology & immunotherapy from Nature Reviews Cancer and Nature Reviews Immunology, together with some recent Research Highlights, describe our progress in understanding the complexity of the immune system in cancer biology and the promise of immunotherapy.
Foreword
Tumour immunotherapy — leukocytes take up the fight
Gemma K. Alderton
&
Yvonne Bordon
doi:10.1038/nri3197
Nature Reviews Immunology 12, 237 (2012)
An introduction to the contents of the joint Focus on Tumour immunology & immunotherapy from Nature Reviews Cancer and Nature Reviews Immunology.
Research Highlights
Immunotherapy: Combinations that work
Sarah Seton-Rogers
doi:10.1038/nrc3250
Nature Reviews Cancer 12, 231 (2012)
Two
papers report preclinical data in support of combining targeted cancer
therapies with immune stimulation mediated by CD137 activation.
Tumour immunology: A close-range dual hit for tumour immunity
Olive Leavy
doi:10.1038/nri3189
Nature Reviews Immunology 12, 227 (2012)
Engineering tumour cells to activate both TLRs and NLRs induces effective antitumour immunity.
Tumour immunogenicity: Editorial selection demystified
Darren J. Burgess
doi:10.1038/nrc3251
Nature Reviews Cancer 12, 227 (2012)
Two studies uncover details of the antigens and immune responses that are involved in the immunoediting of tumours.
Tumour immunology: Suppressing tumorigenic inflammation
Gemma K. Alderton
doi:10.1038/nrc3252
Nature Reviews Cancer 12, 228 (2012)
A
paper uncovers a RAS–RAL GEF signalling pathway that activates AKT and
RAL GTPases to promote survival and motility, and which is inhibited by
the expression of the anti-inflammatory mediator TIPE2.
Tumour immunology: Dendritic cell switch
Sarah Seton-Rogers
doi:10.1038/nrc3253
Nature Reviews Cancer 12, 230-231 (2012)
Jose
Conejo-Garcia and colleagues show that dendritic cells from mice in the
early stages of ovarian tumorigenesis are immunocompetent and hinder
tumour progression, but that they become immunosuppressive in advanced
tumours and promote tumour progression.
T cell memory: Skin-deep memory
Lucy Bird
doi:10.1038/nri3201
Nature Reviews Immunology 12, 227 (2012)
Skin-resident effector memory CD8+ T cells provide long-lasting immune protection in the skin.
In briefs
Tumour immunology: Keeping virus-driven lymphomas in check
Lucy Bird
doi:10.1038/nri3203
Nature Reviews Immunology 12, 231 (2012)
Immunotherapy: A killer combination
Lucy Bird
doi:10.1038/nri3204
Nature Reviews Immunology 12, 231 (2012)
Tumour immunology: Hope in a sticky situation
Yvonne Bordon
doi:10.1038/nri3205
Nature Reviews Immunology 12, 231 (2012)
Reviews
The blockade of immune checkpoints in cancer immunotherapy
Drew M. Pardoll
doi:10.1038/nrc3239
Nature Reviews Cancer 12, 252-264 (2012)
Immune
checkpoints refer to the plethora of inhibitory pathways that are
crucial to maintaining self-tolerance. Tumour cells induce immune
checkpoints to evade immunosurveillance. This Review discusses the
progress in targeting immune checkpoints, the considerations for
combinatorial therapy and the potential for additional immune-checkpoint
targets.
Combining immunotherapy and targeted therapies in cancer treatment
Matthew Vanneman
&
Glenn Dranoff
doi:10.1038/nrc3237
Nature Reviews Cancer 12, 237-251 (2012)
Targeted
therapies can be used to successfully treat cancer patients, but what
are their mechanisms of action? This Review discusses how targeted
therapies modulate the immune system and how they can be rationally
combined with immunotherapies.
Targeting natural killer cells and natural killer T cells in cancer
Eric Vivier, Sophie Ugolini, Didier Blaise, Christian Chabannon & Laurent Brossay
doi:10.1038/nri3174
Nature Reviews Immunology 12, 239-252 (2012)
In
this Review article, the authors describe the mechanisms by which
natural killer cells and natural killer T cells can promote tumour cell
elimination. Furthermore, they discuss the new therapies that are being
used to boost the antitumour properties of these cells in the clinic.
Coordinated regulation of myeloid cells by tumours
Dmitry I. Gabrilovich, Suzanne Ostrand-Rosenberg & Vincenzo Bronte
doi:10.1038/nri3175
Nature Reviews Immunology 12, 253-268 (2012)
Here,
the authors discuss how the immune activities of myeloid cells, such as
macrophages and dendritic cells, are affected by the immunosuppressive
tumour environment. They propose that tumours can evade the immune
system by promoting aberrant differentiation and function of the entire
myeloid system.
Adoptive immunotherapy for cancer: harnessing the T cell response
Nicholas P. Restifo, Mark E. Dudley & Steven A. Rosenberg
doi:10.1038/nri3191
Nature Reviews Immunology 12, 269-281 (2012)
This
article discusses how T cells promote antitumour immunity in patients
with cancer. In certain cancer types, T cell populations that are
isolated from tumours and expanded in vitro can promote cancer
remission when re-infused into patients. The authors explain the pros
and cons of this type of immunotherapy.
Cancer immunotherapy via dendritic cells
Karolina Palucka
&
Jacques Banchereau
doi:10.1038/nrc3258
Nature Reviews Cancer 12, 265-277 (2012)
Dendritic
cells have far-reaching and important effects on the activation of the
immune response; thus, they are used to vaccinate patients with cancer
to induce long-term anti-tumour immunity. This Review discusses what we
know — and need to know — about dendritic cells to improve how they are
used therapeutically.
Antibody therapy of cancer
Andrew M. Scott,
Jedd D. Wolchok
&
Lloyd J. Old
doi:10.1038/nrc3236
Nature Reviews Cancer 12, 278-287 (2012)
The
development of therapeutic antibodies requires a substantial
understanding of cancer serology, protein-engineering techniques,
mechanisms of action and resistance, and the interplay between the
immune system and cancer cells. This Review outlines the fundamental
strategies required to develop antibody therapies for cancer patients.
Perspectives
Unmasking the immune recognition of prostate cancer with CTLA4 blockade
Serena S. Kwek,
Edward Cha
&
Lawrence Fong
doi:10.1038/nrc3223
Nature Reviews Cancer 12, 289-297 (2012)
Cytotoxic
T lymphocyte-associated antigen 4 (CTLA4) represents a crucial immune
checkpoint, the blockade of which can potentiate anti-tumour immunity.
This treatment in patients with advance prostate cancer may provide
insights into the targets that the immune system recognizes to drive
tumour regression.
The immune contexture in human tumours: impact on clinical outcome
Wolf Herman Fridman,
Franck Pagès,
Catherine Sautès-Fridman
&
Jérôme Galon
doi:10.1038/nrc3245
Nature Reviews Cancer 12, 298-306 (2012)
The
infiltration of various types of immune cells is common to most tumour
microenvironments. As discussed in this Opinion article, the pattern of
immune cell infiltration varies between cancer type and individual
tumours of the same type, and this pattern can be used to indicate
prognosis and response to therapy.
The determinants of tumour immunogenicity
Thomas Blankenstein,
Pierre G. Coulie,
Eli Gilboa
&
Elizabeth M. Jaffee
doi:10.1038/nrc3246
Nature Reviews Cancer 12, 307-313 (2012)
Four
leading tumour immunologists provide their opinions on the determinants
of immunogenicity and how we might therapeutically improve tumour
immunogenicity in the future.
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Nature Link: http://www.nature.com/reviews/focus/tumourimmunology/index.html
To read these articles at ISSUU, click here.
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