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Radiation therapy and the innate immune response: Clinical implications for immunotherapy approaches.

ABSTRACT: Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double-strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule-targeted therapies and, in recent years, immunotherapy (IT). Cancer-cell apoptosis after radiation treatment causes an immunological reaction that contributes to eradicating the tumour via antigen presentation and subsequent T-cell activation. By contrast, radiotherapy also contributes to the formation of an immunosuppressive environment that hinders the efficacy of the therapy. Innate immune cells from myeloid and lymphoid origin show a very active role in both acquired resistance and antitumourigenic mechanisms. Therefore, many efforts are being made in order to reach a better understanding of the innate immunity reactions after radiation therapy (RT) and the design of new combinatorial IT strategies focused in these particular populations.

SUBMITTER: Gomez V

PROVIDER: S-EPMC7444780 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Radiation therapy and the innate immune response: Clinical implications for immunotherapy approaches.

Gómez Valentí V Mustapha Rami R Ng Kenrick K Ng Tony T

British journal of clinical pharmacology 20200603 9

Radiation therapy is an essential component of cancer care, contributing up to 40% of curative cancer treatment regimens. It creates DNA double-strand breaks causing cell death in highly replicating tumour cells. However, tumours can develop acquired resistance to therapy. The efficiency of radiation treatment has been increased by means of combining it with other approaches such as chemotherapy, molecule-targeted therapies and, in recent years, immunotherapy (IT). Cancer-cell apoptosis after ra ...[more]

PMID: 32388875

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Project description:BACKGROUND:Three years of treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) trial demonstrated that 2 years of treatment through either route was effective in suppressing the response to nasal allergen challenge, although it was insufficient for inhibition 1 year after discontinuation. OBJECTIVE:We sought to examine in the GRASS trial the time course of immunologic changes during 2 years of sublingual and subcutaneous immunotherapy and for 1 year after treatment discontinuation. METHODS:We performed multimodal immunomonitoring to assess allergen-specific CD4 T-cell properties in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-facilitated allergen binding). RESULTS:All 3 of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years of allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunologic effect. Although frequencies of antigen-specific TH2 cells in peripheral blood determined by using HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE antibody-dependent functional assays remained inhibited in part 1 year after discontinuation. CONCLUSION:Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific TH2 cells most closely paralleled the transient clinical outcome, and it is likely that recurrence of the T-cell drivers of allergic immunity abrogated the potential for durable tolerance. On the other hand, the persistence of IgE blocking antibody 1 year after discontinuation might be an early indicator of a protolerogenic mechanism.

Dataset Information

Radiation therapy and the innate immune response: Clinical implications for immunotherapy approaches.

Publications

Radiation therapy and the innate immune response: Clinical implications for immunotherapy approaches.

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