Immuno-oncology

Immuno-oncology

The tumor microenvironment explained plus research resources

Immuno-oncology is the interaction between the immune system and cancerous cells (tumors). Immuno-oncology research is not only investigating how the immune system reacts to cancerous cells and how the cancerous cells respond, but also how the immune system can be manipulated to effectively target tumors and eradicate them. For detailed information on immuno-oncology read our mini-review entitled “Understanding immuno-oncology – the interplay between the immune system and cancer”.

It is not fully understood exactly how the immune system and the cancerous cells interact with each other within the tumor microenvironment. To aid understanding of this complex process, Dunn et al. (2002) proposed that there are three distinct phases to eventual tumor survival called the three “E” of immunoediting.


Three Stages of Immunoediting

Elimination phase

The immune system is constantly on the lookout for foreign antigen, termed immune surveillance. Upon transformation of normal healthy cells to cancerous cells, specific tumor antigens and cytokines are released which are recognized and responded to as foreign by the immune system. This initial immune response to cancerous cells would typically involve recruitment of cells from the innate immune system such as dendritic cells, macrophages, monocytes and NK cells. Further to this, it is thought that tumor associated neutrophils (TAN) may have an anti-tumor role. The secretion of various cytokines, chemokines and perforin such as interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) related apoptosis inducing ligand (TRAIL), interleukin (IL)-2 and CXCL10 aid cytotoxicity, resulting in apoptosis and tumor cell death. The adaptive immune response, including both T and B cells will then also respond along with associated signaling molecules and together with the innate immune cells launch a co-ordinated fight against the tumor cells, resulting in eradication.

Elimination

Equilibrium phase

During this phase the surviving cancerous cells are held in a steady state. T cells and associated cytokines such as IL-12 and IFN-γ eliminate cancerous cells at the same rate of cancer cell proliferation, thereby limiting tumor growth. This is the longest phase and can last for several years.

Throughout this equilibrium phase, selective pressures on these cancerous cells are at work, resulting in the progression to the escape phase and an increase in tumor heterogeneity.

Equilibrium

Escape phase

The development of non-immunogenic tumor cell variants means that these new type of cancerous cells are able to grow, avoiding the immune response and therefore elimination. The cancerous cells can avoid the immune response in a number of ways, examples include:

  • No longer recognized by the immune system, where antigenicity is not recognized as foreign
    • Mimicking MHC class I molecules
    • Reducing expression of major histocompatibility antigen on cell surface
    • Expressing surface markers preventing NK cell or T cell recognition
    • Releasing proteins that mimic antibodies
  • No longer susceptible to effector mechanisms, such as CD8+ T cells
  • Induce immunosuppression
    • Producing immunosuppressive cytokines like tumor growth factor beta preventing NK cell binding
    • Activating immune check points whose role is to prevent inflammation and ensure homeostasis such as PD-L1 (CD274), CTLA-4 (CD152) and TIM3 (CD366)
    • Signaling to incite the influx of myeloid derived suppressor cells, including TANs and tumor associated macrophages (TAMs), which have been linked with tumor progression. Read our macrophage polarization mini-review for further information on TAMs and the markers associated with different cancer types

This phase results in escape from the immune response and cancer cell growth.

Escape

Key

Key


Resources for Immuno-oncology Research


Learn more about the immune response against cancer


Immuno-oncology mini-review

For detailed information on immuno-oncology including:

  1. Introduction to immuno-oncology
    1. What is immuno-oncology?
    2. Discussion of tumor antigens and function in mediating specificity of anti-tumor immune response
    3. Overview of immune cells involved in anti-tumor immunity and how they mediate tumor control
  2. Overview of cancer immunosurveillance
    1. Three E's
  3. Mechanisms of immunosuppression in cancer
    1. Overview of the various defined mechanisms of immune suppression. E.g. Immune checkpoints and MHC downregulation
    2. Cancer immunotherapy

View mini-review


Cell health products

It is essential to be able to determine the health of normal or cancerous cells.


Antibodies

Bio-Rad provides a comprehensive range of antibodies for immuno-oncology research, either search for these using the filter table below or by entering your marker in the search box at the top of the page.

Find your immuno-oncology antibody

    DescriptionSpecificityTargetFormatHostIsotypeClone Applications Citations Product Type Code

    Reference

    • Dunn GP et al. (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nature Immunol 3, 991-998.