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Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy.

Adachi K, Tamada K - Cancer Sci. (2015)

Bottom Line: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) are typical immune checkpoint molecules intimately involved in the suppression of anti-tumor immunity.Antibodies against those molecules have been developed, such as ipilimumab (anti-CTLA-4 antibody), nivolumab and pembrolizumab (anti-PD-1 antibody), and have been approved by regulatory agencies and used in some countries.Treatment with these antibodies demonstrates previously unobserved clinical efficacies superior to the conventional therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.

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Related in: MedlinePlus

Immunosurveillance and cancer immunoediting. Although gene mutations and resultant generations of cancerous mutant cells routinely occur in a body, the immunosurveillance system detects and eliminates these mutant cells in most cases by trapping them into immunological filters. However, the strong selective pressure by the immune system itself engenders further oncogenic cells, which are inherently immune-resistant and, thus, slip through the immunological filters. Such changes in the immunogenicity of tumors are referred to as cancer immunoediting. Once the mutant cells procure the features with which they prevail over the tumoricidal effects of host immunity, those cells can expand and generate tumors.
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fig01: Immunosurveillance and cancer immunoediting. Although gene mutations and resultant generations of cancerous mutant cells routinely occur in a body, the immunosurveillance system detects and eliminates these mutant cells in most cases by trapping them into immunological filters. However, the strong selective pressure by the immune system itself engenders further oncogenic cells, which are inherently immune-resistant and, thus, slip through the immunological filters. Such changes in the immunogenicity of tumors are referred to as cancer immunoediting. Once the mutant cells procure the features with which they prevail over the tumoricidal effects of host immunity, those cells can expand and generate tumors.

Mentions: The process from the emergence of neoplastic cells to the organization of tumor tissue is one of the most pivotal subjects that has been investigated actively in the field of cancer biology. Regarding tumor–immune system interaction at the initial stage of carcinogenesis (i.e. when the cancerous cells emerge), the following concept has been proposed and widely accepted: gene mutations are unremittingly induced with a constant probability by endogenous or environmental stimuli, so that mutant cells with a potential of carcinogenesis are thought to emerge routinely in vivo. Yet, the host immune system constantly monitors and detects these mutated carcinogenic cells and eliminate them through the mechanism referred to as “cancer immunosurveillance.”22–24 However, through accumulated emergence of the mutated cells, some of them incidentally acquire the capacity to evade immunosurveillance (i.e. avoiding a clearance by the host immune system), and continue their expansion to establish the organization of tumor tissue. Those changes in the immunogenicity of tumor cells, which result from continuous pressure against the tumors by the host immune system and the consequent occurrence of the mutants resistant to the immunosurveillance, are referred to as “cancer immunoediting” (Fig.1).23–25 In other words, cancers that we observe in clinical settings as a detectable mass have already evaded anti-tumor immunity by editing immunogenicity from the initial stage of carcinogenesis, while the frequency of the mutations (i.e. the number and/or the repertoire of neoantigens) varies among the tumor types.26,27 Accordingly, immune resistance is inherent in the nature of established cancers.


Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy.

Adachi K, Tamada K - Cancer Sci. (2015)

Immunosurveillance and cancer immunoediting. Although gene mutations and resultant generations of cancerous mutant cells routinely occur in a body, the immunosurveillance system detects and eliminates these mutant cells in most cases by trapping them into immunological filters. However, the strong selective pressure by the immune system itself engenders further oncogenic cells, which are inherently immune-resistant and, thus, slip through the immunological filters. Such changes in the immunogenicity of tumors are referred to as cancer immunoediting. Once the mutant cells procure the features with which they prevail over the tumoricidal effects of host immunity, those cells can expand and generate tumors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4556381&req=5

fig01: Immunosurveillance and cancer immunoediting. Although gene mutations and resultant generations of cancerous mutant cells routinely occur in a body, the immunosurveillance system detects and eliminates these mutant cells in most cases by trapping them into immunological filters. However, the strong selective pressure by the immune system itself engenders further oncogenic cells, which are inherently immune-resistant and, thus, slip through the immunological filters. Such changes in the immunogenicity of tumors are referred to as cancer immunoediting. Once the mutant cells procure the features with which they prevail over the tumoricidal effects of host immunity, those cells can expand and generate tumors.
Mentions: The process from the emergence of neoplastic cells to the organization of tumor tissue is one of the most pivotal subjects that has been investigated actively in the field of cancer biology. Regarding tumor–immune system interaction at the initial stage of carcinogenesis (i.e. when the cancerous cells emerge), the following concept has been proposed and widely accepted: gene mutations are unremittingly induced with a constant probability by endogenous or environmental stimuli, so that mutant cells with a potential of carcinogenesis are thought to emerge routinely in vivo. Yet, the host immune system constantly monitors and detects these mutated carcinogenic cells and eliminate them through the mechanism referred to as “cancer immunosurveillance.”22–24 However, through accumulated emergence of the mutated cells, some of them incidentally acquire the capacity to evade immunosurveillance (i.e. avoiding a clearance by the host immune system), and continue their expansion to establish the organization of tumor tissue. Those changes in the immunogenicity of tumor cells, which result from continuous pressure against the tumors by the host immune system and the consequent occurrence of the mutants resistant to the immunosurveillance, are referred to as “cancer immunoediting” (Fig.1).23–25 In other words, cancers that we observe in clinical settings as a detectable mass have already evaded anti-tumor immunity by editing immunogenicity from the initial stage of carcinogenesis, while the frequency of the mutations (i.e. the number and/or the repertoire of neoantigens) varies among the tumor types.26,27 Accordingly, immune resistance is inherent in the nature of established cancers.

Bottom Line: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) are typical immune checkpoint molecules intimately involved in the suppression of anti-tumor immunity.Antibodies against those molecules have been developed, such as ipilimumab (anti-CTLA-4 antibody), nivolumab and pembrolizumab (anti-PD-1 antibody), and have been approved by regulatory agencies and used in some countries.Treatment with these antibodies demonstrates previously unobserved clinical efficacies superior to the conventional therapies.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.

Show MeSH
Related in: MedlinePlus