On the Immunological Consequences of Conventionally Fractionated Radiotherapy

Alfonso, Juan Carlos López; Papaxenopoulou, Lito A.; Mascheroni, Pietro; Meyer‐Hermann, Michael; Hatzikirou, Haralampos

doi:10.1016/j.isci.2020.100897

Cited by 18 publications

(16 citation statements)

References 60 publications

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“…Receptor of angiotensin‐converting enzyme 2 (ACE2) and transmembrane protease serine 2 are critical for SARS‐CoV‐2 cell entry and are highly expressed on prostate cancer cells [13], making these cells vulnerable to SARS‐CoV‐2 infection. It is possible that radiation triggered immunogenic cell death of the prostate cancer cells (potentially infected with SARS‐CoV‐2), leading to release of damage‐ or pathogen‐associated molecular patterns [40] related to SARS‐CoV‐2 and allowing the development of both an early innate (based on monocytes and macrophages, that are more radioresistant than other immune cells [38], proliferation) and adaptive immune response. Evidence of increased antibody production in patients with head and neck cancer subjected to definitive radiation (with lysis of tumor cells and exposure of intracellular content to antigen‐presenting cells) has been described [41].…”

Section: Discussionmentioning

confidence: 99%

Humoral Immune Response ofSARS-CoV-2–Infected Patients with Cancer: Influencing Factors and Mechanisms

et al. 2021

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Background. SARS-CoV-2 infected cancer patients (CP) show worse outcomes compared with non-cancer patients (NCP). The humoral immune response (HIR) of CP against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized SARS-CoV-2 CP. Materials and Methods. Unicentric, retrospective study enrolling adult SARS-CoV-2 patients admitted to a central hospital from March 15 to June 17, 2020, whose serum samples were quantified for anti-SARS-CoV-2 receptorbinding domain or spike protein immunoglobulin (Ig) M, G and A antibodies. The aims of the study were to assess the HIR to SARS-CoV-2, correlate it with different cancer types, stages and treatments, clarify the interplay between HIR of CP and clinical outcomes and to compare the HIR of SARS-CoV-2 CP and NCP. Results. We included 72 SARS-CoV-2 positive subjects (19 CP, 53 controls). About 90% of controls revealed a robust serological response. Among CP, a strong response was verified in 57.9% of them, with 42.1% showing a persistently weak response. Treatment with chemotherapy within 14 days before positivity was the only factor statistically shown to be associated with persistently weak serological responses among CP. No significant differences in outcomes were observed between CP with strong and weak responses. All IgG, IgM, IgA and total Ig antibody titers were significantly lower in CP when compared with NCP. Conclusions. A significant part of CP develops a proper HIR. Recent chemotherapy treatment may be associated with weak serological responses among CP. CP have a weaker SARS-CoV-2 antibody response compared with NCP. Implications for practice. Our results place the spotlight on cancer patients, particularly the ones actively treated with chemotherapy. These patients may potentially be more vulnerable to SARS-CoV-2 infection, being important to provide oncologists further theoretical support (with concrete examples and respective mechanistic correlations) for the decision of starting, maintaining or stopping antineoplastic treatments (particularly chemotherapy) not only on noninfected but also on infected cancer patients in accordance with cancer type, stage and prognosis, treatment agents, treatment setting and SARS-CoV-2 infection risks. The Oncologist ;9999:• •

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Section: Discussionmentioning

confidence: 99%

Humoral Immune Response ofSARS-CoV-2–Infected Patients with Cancer: Influencing Factors and Mechanisms

et al. 2021

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“…The optimal schedule for combining radiotherapy and IO is not completely clear and may depend on the type of IO used. Namely, fRT can lead to overtreatment of patients due to the “one-size-fits-all” dose scheduling, because antitumor immunity can be mitigated after a number of fractions [ 98 ]. Moreover, dose scheduling will affect immune infiltration, which should be considered as an important factor determining IO efficacy.…”

Section: Window Of Opportunity To Achieve Synergy Between Radiothementioning

confidence: 99%

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Marcus

Lieverse

Klein

et al. 2021

Cancers

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Radiotherapy (RT) has been shown to interfere with inflammatory signals and to enhance tumor immunogenicity via, e.g., immunogenic cell death, thereby potentially augmenting the therapeutic efficacy of immunotherapy. Conventional RT consists predominantly of high energy photon beams. Hypofractionated RT regimens administered, e.g., by stereotactic body radiation therapy (SBRT), are increasingly investigated in combination with cancer immunotherapy within clinical trials. Despite intensive preclinical studies, the optimal dose per fraction and dose schemes for elaboration of RT induced immunogenic potential remain inconclusive. Compared to the scenario of combined immune checkpoint inhibition (ICI) and RT, multimodal therapies utilizing other immunotherapy principles such as adoptive transfer of immune cells, vaccination strategies, targeted immune-cytokines and agonists are underrepresented in both preclinical and clinical settings. Despite the clinical success of ICI and RT combination, e.g., prolonging overall survival in locally advanced lung cancer, curative outcomes are still not achieved for most cancer entities studied. Charged particle RT (PRT) has gained interest as it may enhance tumor immunogenicity compared to conventional RT due to its unique biological and physical properties. However, whether PRT in combination with immune therapy will elicit superior antitumor effects both locally and systemically needs to be further investigated. In this review, the immunological effects of RT in the tumor microenvironment are summarized to understand their implications for immunotherapy combinations. Attention will be given to the various immunotherapeutic interventions that have been co-administered with RT so far. Furthermore, the theoretical basis and first evidences supporting a favorable immunogenicity profile of PRT will be examined.

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“…Alfonso et al. ( 27 ) suggested a model for the immune modulatory effect of fractionated radiation. It starts off from a quite detailed model of tumor growth dynamics, accounting for hypoxic avascular and potentially necrotic regions inside the tumor.…”

Section: Model Approachesmentioning

confidence: 99%

Modeling Radioimmune Response—Current Status and Perspectives

2021

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The combination of immune therapy with radiation offers an exciting and promising treatment modality in cancer therapy. It has been hypothesized that radiation induces damage signals within the tumor, making it more detectable for the immune system. In combination with inhibiting immune checkpoints an effective anti-tumor immune response may be established. This inversion from tumor immune evasion raises numerous questions to be solved to support an effective clinical implementation: These include the optimum immune drug and radiation dose time courses, the amount of damage and associated doses required to stimulate an immune response, and the impact of lymphocyte status and dynamics. Biophysical modeling can offer unique insights, providing quantitative information addressing these factors and highlighting mechanisms of action. In this work we review the existing modeling approaches of combined ‘radioimmune’ response, as well as associated fields of study. We propose modeling attempts that appear relevant for an effective and predictive model. We emphasize the importance of the time course of drug and dose delivery in view to the time course of the triggered biological processes. Special attention is also paid to the dose distribution to circulating blood lymphocytes and the effect this has on immune competence.

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On the Immunological Consequences of Conventionally Fractionated Radiotherapy

Cited by 18 publications

References 60 publications

Humoral Immune Response ofSARS-CoV-2–Infected Patients with Cancer: Influencing Factors and Mechanisms

Humoral Immune Response ofSARS-CoV-2–Infected Patients with Cancer: Influencing Factors and Mechanisms

Charged Particle and Conventional Radiotherapy: Current Implications as Partner for Immunotherapy

Modeling Radioimmune Response—Current Status and Perspectives

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