Elements of cancer immunity and the cancer–immune set point

  title={Elements of cancer immunity and the cancer–immune set point},
  author={Daniel S Chen and Ira Mellman},
Immunotherapy is proving to be an effective therapeutic approach in a variety of cancers. But despite the clinical success of antibodies against the immune regulators CTLA4 and PD-L1/PD-1, only a subset of people exhibit durable responses, suggesting that a broader view of cancer immunity is required. Immunity is influenced by a complex set of tumour, host and environmental factors that govern the strength and timing of the anticancer response. Clinical studies are beginning to define these… 

Predictors of Response to Immune Checkpoint Blockade

A deep understanding of responses to immune checkpoint blockade pivots on a fundamental knowledge of antitumor immune responses, which are influenced by numerous factors in the tumor itself, in the tumors microenvironment, in host immunity, and in the local and extended environment.

Immune oncology, immune responsiveness and the theory of everything

A strategy to integrate compelling data from various paradigms into a “Theory of Everything” is proposed and the creation of a task force aimed at systematically addressing salient questions relevant to cancer immune responsiveness and immune evasion is proposed.

Lessons learned from the blockade of immune checkpoints in cancer immunotherapy

The current understanding of the mechanisms by which resistance to checkpoint blockade immunotherapy occurs is summarized, and how actionable combination strategies may be derived to improve clinical outcomes for patients is outlined.

Complementing the Cancer-Immunity Cycle

Evidence is provided to support the idea that complement blocks many of the effector routes associated with the cancer-immunity cycle, providing the rationale for new therapeutic combinations aimed to enhance the antitumor efficacy of anti-PD-1/PD-L1 checkpoint inhibitors.

The hallmarks of successful anticancer immunotherapy

The hallmarks of successful anticancer immunotherapy are outlined, including the type, density, localization, and functional orientation of the immune infiltrate, as do features of the tumor microenvironment linked to the vasculature and stroma, and systemic factors including the composition of the gut microbiota.

T lymphocyte subsets in cancer immunity: Friends or foes

The central role of the mainly antitumor subsets, cytotoxic T cells and Th1 cells, will be delineated and how other subsets including Th2, Th17, and T regulatory cells exhibit ambivalent roles are indicated.

Hallmarks of response to immune checkpoint blockade

The foundation for pillars and hallmarks of response to immune checkpoint blockade are described, with a discussion of their relevance to immune monitoring and mechanisms of resistance.

Targeting T cell activation in immuno-oncology.

The basic biology of T cell activation is reviewed, with particular emphasis on the essential role of the dendritic cell and the innate immune system in T cellactivation.

Checkpoint blockade‐based immunotherapy in the context of tumor microenvironment: Opportunities and challenges

A modified classification of TME is proposed, and optimized TME classification is needed through detailed and integrated molecular characterization of large patient cohorts in the future to improve cancer immunotherapy.



Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy

It is demonstrated that immunoselection by CD8+ T cells of tumor variants lacking strong tumor‐specific antigens represents one mechanism by which cancer cells escape tumor immunity and points toward the future of personalized cancer therapy.

Neoantigens in cancer immunotherapy

Observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens.

The blockade of immune checkpoints in cancer immunotherapy

  • D. Pardoll
  • Biology, Medicine
    Nature Reviews Cancer
  • 2012
Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

Therapeutic vaccines for cancer: an overview of clinical trials

An overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens is provided and their implications for the use of active immunotherapy are discussed.

The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition

The concept of the tumor immunity continuum is proposed as a framework for developing rational combination strategies for anticancer immune therapies based on current understanding of tumor and circulating pharmacodynamic correlates of immune modulation.

Innate immune recognition of cancer.

A deeper knowledge of the clinically relevant innate immune pathways involved in the recognition of tumors is leading toward new therapeutic strategies for cancer treatment.

Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens

Tumour-specific mutant proteins are identified as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and it is shown that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy.