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.


Tumour immunotherapy — leukocytes take up the fight

Gemma K. Alderton & Yvonne Bordon


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


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


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


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


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


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


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


Nature Reviews Immunology 12, 231 (2012)

Immunotherapy: A killer combination

Lucy Bird


Nature Reviews Immunology 12, 231 (2012)

Tumour immunology: Hope in a sticky situation

Yvonne Bordon


Nature Reviews Immunology 12, 231 (2012)


The blockade of immune checkpoints in cancer immunotherapy

Drew M. Pardoll


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


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


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


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


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


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


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.


Unmasking the immune recognition of prostate cancer with CTLA4 blockade

Serena S. Kwek, Edward Cha & Lawrence Fong


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


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


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.