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Published on: November 28, 2019
Modulation of antitumor immune responses
1Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Abstract:
Based on experimentation in animal model systems it is reasonable to expect immunomodulation by anticancer drugs and biological response modifiers to be instrumental in at least some of the antitumor effects of such agents. Even in the defined animal models, however, the immunomodulating effects of any given agent are in most cases correlated only with the therapeutic response to that agent, whereas causal relationships still evade unequivocal demonstration. The difficulties in this respect are magnified in humans, in whom the very nature and regulation of antitumor immunity, taken in a broad sense, are not yet well defined; thus at this time the basis on which to interpret the therapeutic or toxicological causative relevance of an immunomodulating effect is insufficient. Despite these limitations and uncertainties, or perhaps responding to the challenge they provide, experimentation evaluating the potential of immunomodulation is being carried out in a number of diversified areas. Salient findings from selected investigations of the actions of 1) drugs, 2) cytokines, and 3) combinations of agents or effectors are discussed as examples of the realization of the potential of this overall approach as well as to outline the requirements for future development of biological response modifiers.
Insights
Anticancer drugs and biological response modifiers show potential for immunomodulation in cancer therapy. However, definitively proving the causal link between immunomodulatory effects and therapeutic outcomes remains challenging in both animal models and humans.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Anticancer drugs and biological response modifiers (BRMs) are hypothesized to exert antitumor effects via immunomodulation.
- While animal models suggest a correlation between immunomodulation and therapeutic response, causal relationships are difficult to establish definitively.
- The complexity of human antitumor immunity and its regulation further complicates the interpretation of immunomodulatory effects in cancer patients.
Purpose of the Study:
- To review and discuss findings from investigations into the immunomodulatory potential of anticancer agents.
- To explore the role of immunomodulation in the therapeutic effects of drugs, cytokines, and combination therapies.
- To outline future requirements for the development of effective biological response modifiers.
Main Methods:
- Review of experimental findings from animal model systems and human studies.
- Analysis of the immunomodulatory actions of anticancer drugs.
- Examination of the effects of cytokines and combined therapeutic agents on antitumor immunity.
Main Results:
- Immunomodulation by anticancer agents is a recognized phenomenon, particularly in animal models.
- Establishing a direct causal link between immunomodulation and therapeutic efficacy remains a significant challenge.
- Research is ongoing across diverse areas, exploring various agents and combinations for their immunomodulatory potential.
Conclusions:
- Despite challenges in demonstrating causality, immunomodulation holds promise for cancer treatment.
- Further research is needed to elucidate the mechanisms and optimize the application of immunomodulatory agents.
- Development of biological response modifiers requires a clear understanding of their impact on antitumor immunity.
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