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Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response
1Department of Cell Biology and Kaplan Cancer Center, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA. freya01@med.nyu.edu
Abstract:
Growth of cancer in rodent models and in patients elicits immune responses directed toward various antigens expressed by the transformed cell. Clearly though, as most tumors grow, unmanipulated antitumor immune responses are incapable of eliminating cancer. Over the past approximately 15 years, antitumor immunoglobulin and T cells have been used to identify tumor antigens, which in turn, have served as the basis for therapeutic vaccine trials. However, experimental cancer vaccines, although in some patients result in elimination of large tumor burdens, have a low frequency of long-term cancer remission in most patients, ca. <5%. Therefore, as tumors express antigens that distinguish themselves from nontransformed cells in immunological terms (i.e., elicit immune responses to growth of primary tumor and can target tumor cells in vivo), and tumor vaccines prime unsuccessful antitumor immune responses in patients, it is likely that growth of cancer induces immune tolerance to tumor cells. Although there are several types of T cell tolerance, mature, antigen-specific CD8+ T cells isolated from tumors are lytic-defective, implying that the tumor microenvironment inactivates the antitumor effector phase. The nature of the functional local tolerance to antitumor immune response is the subject of this review.
Insights
Cancer growth triggers immune responses, but most tumors evade elimination. This review explores how the tumor microenvironment causes immune tolerance, hindering effective cancer immunotherapy and leading to low remission rates.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Tumor growth in rodent models and patients activates immune responses against cancer-specific antigens.
- Despite immune engagement, most tumors are not eliminated by natural antitumor immunity.
- Therapeutic cancer vaccines, developed over 15 years, show limited long-term remission rates (<5%) in patients.
Purpose of the Study:
- To investigate the mechanisms by which tumors induce immune tolerance.
- To understand the inactivation of antitumor immune responses within the tumor microenvironment.
- To review the nature of local functional tolerance to antitumor immunity.
Main Methods:
- Review of existing literature on tumor immunology and immunotherapy.
- Analysis of immune responses, including T cell activity, in cancer models and patients.
- Examination of tumor antigens and their role in immune evasion.
Main Results:
- Tumors express antigens that elicit immune responses but are not eliminated by them.
- Cancer vaccines demonstrate low efficacy in achieving long-term remission.
- Mature, tumor-infiltrating CD8+ T cells are functionally impaired (lytic-defective).
Conclusions:
- Cancer growth likely induces immune tolerance to tumor cells.
- The tumor microenvironment plays a critical role in inactivating the effector phase of antitumor immunity.
- Understanding local immune tolerance is crucial for developing more effective cancer therapies.
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