Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

学位記番号：医博乙140

TREATMENT PATTERNS, HEALTHCARE RESOURCE UTILIZATION, AND OUTCOMES FOR EARLY STAGE TRIPLE-NEGATIVE BREAST CANCER IN JAPAN - supplementary material

Table S1. List of anti-HER2 and hormone therapiesFigure S2. Patient disposition (hospital claims data)Figure S3. Patient disposition (health insurance claims data)Figure S4. Kaplan–Meier plots of overall survival in patients with early stage breast cancer (Groups 1 and 2)Figure S5. Kaplan–Meier plots of event-free survival in patients with early stage breast cancer (Groups 1 and 2)</p

Anti-tumor immune responses induced by radiotherapy: a review

An anti-tumor immune response is one of the most important factors that can determine treatment response and prognosis of cancer patients. Recent studies have demonstrated that radiotherapy can activate tumor-specific immune responses and that these responses contribute to the therapeutic efficacy. However, the exact mechanisms underlying the radiation-induced immune responses remain unclear. Better understanding of the mechanisms could facilitate the application of immune-activating radiotherapy and provide new treatment strategies. We previously demonstrated that tumor-specific T cell responses could be induced in esophageal cancer patients during and after chemoradiotherapy. Furthermore, in a mouse model, immune responses played an important role in determining the local and systemic therapeutic efficacy of radiotherapy that could be augmented by the immune checkpoint blockade. In this review, radiotherapy-induced immune responses, the mechanisms underlying the induction of those responses, and a practical application of the therapy are discussed

High linear energy transfer carbon-ion irradiation increases the release of the immune mediator high mobility group box 1 from human cancer cells.

Anti-tumor immunity modulates the local effects of radiation therapy. High mobility group box 1 (HMGB1) plays a pivotal role in activating antigen-specific T-cell responses. Here, we examined the relationship between linear energy transfer (LET) and HMGB1 release. We assessed the proportions of KYSE-70, HeLa and SiHa cells surviving after carbon-ion (C-ion) beam irradiation with different LET values, using a clonogenic assay. The D10, the dose at which 10% of cells survived, was calculated using a linear-quadratic model. HMGB1 levels in the culture supernatants of C-ion beam-irradiated tumor cells were assessed by enzyme-linked immunosorbent assay. The D10 doses for 13 keV/μm of C-ion irradiation in KYSE-70, HeLa and SiHa cells were 2.8, 3.9 and 4.1 Gy, respectively, whereas those for 70 keV/μm C-ion irradiation were 1.4, 1.9 and 2.3 Gy, respectively. We found that 70 keV/μm of C-ion irradiation significantly increased HMGB1 levels in the culture supernatants of all cell lines 72 h after irradiation compared with non-irradiated controls. Furthermore, 70 keV/μm of C-ion irradiation significantly increased HMGB1 levels in the culture supernatants of all cell lines 72 h after irradiation compared with 13 keV/μm. The results suggest that HMGB1 release from several cancer cell lines increases with increased LET

Hyperacute ischemic stroke treated with carotid-carotid artery bypass surgery “case report”

Thrombolytic therapy using heparin, urokinase, and tissue plasminogen activator (tPA) has been the standard treatment for hyperacute ischemic stroke (HIS) with worsening carotid artery stenosis. In recent years, endovascular treatments (thrombectomy and carotid artery stenting) have attracted attention, and neurosurgeons are increasingly participating in these treatments. A 70-year-old Japanese male presented to our hospital with aphasia and right hemiparesis. Emergency computed tomography ([CT] CT angiography and perfusion CT) revealed a small infarct core and a large hemiparesis due to occlusion near the left common carotid artery orifice. Because of hemorrhagic sequelae, tPA was not administered, and emergency endovascular treatment failed. Therefore, a bilateral common carotid artery bypass surgery was performed. Revascularization was performed within 51 min of the start of the surgery, and the time from onset to revascularization was 5 h. Aphasia and right hemiparesis resolved immediately after surgery. The only sequela observed was mild dyskinesia. Our report is the first to show that bilateral common carotid artery bypass is a novel and effective treatment for HIS

Anti‐PD‐1 monoclonal antibody‐resistant esophageal squamous cell carcinoma showing the abscopal effect: A case report with T‐cell receptor/B‐cell receptor repertoire analysis

Abstract Background Several clinical trials of nivolumab have reported good results, including those in patients with advanced esophageal squamous cell carcinoma. However, the response rate of this drug remains poor. Notably, a rare phenomenon called abscopal effect refers to the regression of irradiated and nonirradiated distant tumors after local radiotherapy. Although the mechanism of this effect remains unclear, the antitumor immunity induced by radiotherapy is considered to be the most important factor. Case A 66‐year‐old man with recurrent nivolumab‐resistant esophageal squamous cell carcinoma along with left‐side cervical and abdominal para‐aortic lymph node metastases was treated with a 40 Gy (10 fractions) dose of radiotherapy to the left‐side cervical lymph node metastasis as a palliative treatment, which caused neck pain. In addition, nivolumab administration was resumed the day after completion of radiotherapy. Three months after radiotherapy, the irradiated lesion on the left neck had regressed to a scar‐like lesion. Furthermore, the previously progressive abdominal para‐aortic lymph nodes outside the irradiation area shrank (abscopal effect). T‐cell receptor and B‐cell receptor (TCR/BCR) repertoire analyses before and after radiotherapy revealed that radiotherapy led to changes in the TCR/BCR repertoire. Conclusion Changes in the TCR/BCR repertoire may be a part of the mechanism underlying the abscopal effect. The findings of the present case suggest that the combination of immune checkpoint inhibitors and radiotherapy is a promising treatment approach even for patients with immune checkpoint inhibitor‐resistant cancer