immunology & radiobiology

OBJECTIVE: to evaluate the subpopulation structure of peripheral blood leukocytes as a component of inflammaging in the servicemen of the Armed Forces of Ukraine and clean-up workers of the accident at the Chornobyl nuclear power plant. MATERIALS AND METHODS: Three hundred ninety-seven males aged 30-82 (54.99 ± 8.85) years examined. Among them: clean-up workers of the accident at the Chornobyl nuclear power plant, aged 54-64 (59.95 ± 1.88) years, who were examined before the beginning and during the Russian military invasion of Ukraine; 24 civilians of the control group, aged 50-77 (58...

PURPOSE: The capability of ultrahigh dose rate FLASH radiation therapy to generate the FLASH effect has opened the possibility to enhance the therapeutic index of radiation therapy. The contribution of the immune response has frequently been hypothesized to account for a certain fraction of the antitumor efficacy and tumor kill of FLASH but has yet to be rigorously evaluated. METHODS AND MATERIALS: To investigate the immune response as a potentially important mechanism of the antitumor effect of FLASH, various murine tumor models were grafted either subcutaneously or orthotopically into immunocompetent mice or in moderately and severely immunocompromised mice...

OBJECTIVE: This study assessed perceived barriers, precancerous cervical lesion screening acceptance, and associated factors among women in Eastern Ethiopia. SETTING: This study was conducted in Hiwot Fana Specialized Hospital and Jugal Hospital. STUDY DESIGN: This study is a facility-based cross-sectional study. STUDY PARTICIPANTS: This study included 1181 women aged 25-49 years. Bivariate and multivariable logistic regression was used to evaluate the relationship between variables and control confounders...

On August 10, 2023, an outstanding Ukrainian scientist, Doctor of medical sciences, Professor, pathophysiologist, oncoimmunologist, laureate of the State Prize of Ukraine in the field of science and technology and laureate of the priz- es of the NASU named after I.I. Mechnikov, R.E. Kavetsky, and O.O. Bohomolets, the leading scientist of the Labora- tory of Oncoimmunology and Antitumor Vaccine Design of R.E. Kavetsky Institute of Experimental Pathology, On- cology and Radiobiology of the NASU Ninel Mykhailivna Berezhna passed away...

PURPOSE/OBJECTIVE(S): The effect of cancer treatment on immunologic decline and recovery in people with HIV (PWH) is not well-described. This study aims to describe the trajectory of treatment-related immunosuppression in PWH treated for HNC predominantly with radiotherapy with or without chemotherapy and/or surgery. MATERIALS/METHODS: We performed a retrospective chart review of 23 PWH diagnosed with nonmetastatic HNC at our institution between 2002 and 2020. Baseline and longitudinal changes in CD4 count from the time of cancer treatment initiation were investigated...

PURPOSE/OBJECTIVE(S): ROR1771 was a clinical trial investigating the use of stereotactic body proton radiotherapy (SBPT) and nivolumab in recurrent platinum refractory head and neck squamous cell carcinoma (HNSCC). The planned analysis of T-cell subpopulation and biomarker response is herein presented. MATERIALS/METHODS: Patients with metastatic histologically confirmed HNSCC from any primary site received 2 cycles of nivolumab followed by SBPT to 1-2 selected target lesion(s) (hilar/lung: 8 of 12 patients), followed by maintenance nivolumab...

PURPOSE/OBJECTIVE(S): The optimal sequencing of stereotactic ablative body radiotherapy (SABR) with anti-PD1 checkpoint blockade is unknown. The purpose of SABRseq was to assess the toxicity of the combination of SABR delivered either before or after the commencement of pembrolizumab. The central hypothesis is that the treatment combination will have a safety profile that is clinically acceptable and demonstrate anti-tumor efficacy. Furthermore, we hypothesize that differences in systemic immune activation will be observed between treatment arms...

PURPOSE/OBJECTIVE(S): Anal cancer disproportionately affects PWH despite antiretroviral therapy. Data on CRT outcomes are limited. Modern IMRT CRT decreases acute toxicity but may exacerbate immune dysregulation from chronic HIV. Although historical CRT has been associated with prolonged CD4 count suppression, little is known about late immunotoxicity in PWH after contemporary CRT. We report clinical outcomes and long term immunotoxicity. MATERIALS/METHODS: Single-center retrospective review of all PWH confirmed on chart review with anal squamous cell carcinoma without prior pelvic irradiation treated with definitive IMRT CRT...

PURPOSE/OBJECTIVE(S): Considering the therapeutic toxicity, the question of how to administer adequate chemotherapy to synchronize Stereotactic body radiation therapy (SBRT) treatment strategy for maximizing the benefits of neoadjuvant therapy to improve prognosis is a challenging and debatable issue. This study explores the feasibility and theoretical advantages of the simultaneous implementation of split-course SBRT with systemic treatment. MATERIALS/METHODS: We evaluated the effect of three irradiation regimens (conventional radiotherapy (C-R, 15×2 Gy, (D1-5, D8-12, D15-19)), continuous SBRT (C-S, 3×7 Gy, (D1-3)), split SBRT (S-S, 3×7 Gy, (D1, D10, D19)) in combination with systemic therapy (chemotherapy (gemcitabine), PD-1 inhibitor (Anti-mouse PD-1 antibody) and angiogenesis-targeting agent (Anlotinib)) on tumor growth and survival by using the immunologically active C57BL/6 bilateral subcutaneous model with different cancer cells...

PURPOSE/OBJECTIVE(S): Targeting PD-L1 is a beneficial strategy to reinvigorate antitumor immunity, however variable response and resistance are challenging and suggest the need for multimodality approaches. Tumor cell-intrinsic PD-L1 signals also regulate non-canonical pathogenic pathways that may impact treatment resistance. Ionizing radiation (IR) can induce antitumor immunity and has demonstrated therapeutic synergy with immunotherapy in some cases, however tumor-driven immunologic mechanisms affecting clinical outcomes remain incompletely understood...

PURPOSE/OBJECTIVE(S): Whole-lung, low-dose radiation (LD-RT) for COVID-19 requires randomization and biologic correlates to determine causality and mechanism. MATERIALS/METHODS: A phase III trial randomized COVID-19 patients to physician's choice of drug therapy with or without LD-RT. Primary endpoint was intubation-free survival (IFS). The trial was designed with 80% power (two-sided log rank, alpha 0.05) to detect a hazard ratio of 0.3 after 12 intubation events...

PURPOSE/OBJECTIVE(S): Immunotherapies, such as immune checkpoint inhibitors (ICIs), have revolutionized management of some cancers but have little benefit for microsatellite-stable colorectal cancer patients (MSS-CRC). This is, in part, due to the low mutations and neoantigen expression in this immunogenically "cold" MSS-CRC. Therefore, we aim to develop novel shared neoantigen-based therapeutic cancer vaccine to reinvigorate antitumor immunity and enhance the therapeutic benefit of radiotherapy in MSS-CRC...

PURPOSE/OBJECTIVE(S): Recently, multiple clinical trials have demonstrated success of PD-1/PD-L1-targeted immune checkpoint inhibition (ICI) in recurrent and metastatic head and neck cancer (HNC). However, three large clinical trials combining PD-1/PD-L1-targeted ICI with RT or chemo-RT (CRT) in the definitive management of HNC have shown no benefit of combination therapy with ICI over RT or CRT alone. Our overarching hypotheses are: i) hypo-fractionation may ultimately better synergize with ICI compared to conventional RT regimens, and ii) immunologic changes in the tumor microenvironment may be detectable using quantitative MRI (qMRI) parameters collected during RT...

PURPOSE/OBJECTIVE(S): Despite advances in multidisciplinary care, the risk of late recurrence in Estrogen Receptor-positive (ER+) breast cancer (BC) patients following standard-of-care treatment ranges from 20-52% at 20 years. While immune checkpoint inhibitors (CPI), have shown enormous potential in inducing long term remission in some cases, patients with ER+ BC show poor response to these agents. The objective of this study is to develop effective radiation therapy (RT)-based combination regimens that induce anti-tumor immunity against immunologically cold ER+ breast tumors...

PURPOSE/OBJECTIVE(S): Preclinical studies suggest that radiotherapy (RT) elicits various effects on antitumor T-cell responses. However, systemic T-cell responses upon RT in real-world cancer patients, including those with metastatic breast cancer, are poorly characterized. This study aims to investigate the detailed dynamics of peripheral T cells upon stereotactic body radiotherapy (SBRT) in metastatic breast cancer patients. MATERIALS/METHODS: Peripheral blood samples of 32 prospectively recruited patients who received SBRT to bone metastasis of breast cancer, which were acquired at pre-SBRT (W0), 1 week after SBRT (W1), and 4 weeks after SBRT (W4), were analyzed using multi-color flow cytometry and cytometric bead array...

PURPOSE/OBJECTIVE(S): Persistent infection of human papillomavirus (HPV) is one major etiology of cervical cancer (CC). By now, anti-PD-1 immunotherapy is approved for advanced CC patients, but the response rate was just about 10-20%, tumor immune microenvironment (TIME) might be one factor that affect the efficacy. The indoleamine 2,3-dioxygenase (IDO), a metabolic immune checkpoint, is recently shown to have a correlation-ship with HPV carcinogenesis in CC, with unknown mechanism. This study, using the single cell transcriptomic single-cell sequencing and spatial transcription sequencing analysis/immunologic technology, aimed to exam the role of IDO1 expression in HPV+ CC TIME and explore the changes after radiotherapy...

PURPOSE/OBJECTIVE(S): A radiation boost targeted at the tumor bed is an important component of breast-conserving therapy (BCT) and has been shown to improve outcomes in patients with early-stage breast cancer. This is a prospective phase II study (NCT04871516) to assess the feasibility of delivering the radiation boost pre-operatively. This approach allows more accurate targeting of the high radiation dose at the tumor that may spare more normal breast tissue. We hypothesize wound complication rates to be comparable to standard treatment...

PURPOSE/OBJECTIVE(S): Relapsed, refractory multiple myeloma is associated with poor outcome. Role of radiotherapy is mainly for palliation. Anti-PD1 inhibitors have failed to show efficacy in relapsed refractory myeloma patients. A phase 2 trial (NCT03267888) was conducted to see if radiotherapy (8 Gy in 1 fraction) and anti-PD1 (Pembrolizumab) could provide early signals of safety and response. MATERIALS/METHODS: A prospective single-center phase 2 trial involving patients >18 years of age with ECOG 0-1 was conducted after obtaining IRB approval...

PURPOSE/OBJECTIVE(S): The tumor microenvironment (TME) in HPV-unrelated head and neck cancer (HNC) is considered to be immunologically "cold," and immunometabolic adaptations to radiotherapy (RT) can exacerbate these conditions and lead to radioresistance. Peroxisome proliferator-activated receptor-α (PPARα) agonism may improve the immune response to RT by reducing glucose scarcity through upregulation of fatty acid utilization in cancer cells. Our clinical trial data shows that high serum oleic acid (OA), a PPAR ligand, correlates with response to radioimmunotherapy...

One of the most important therapeutic interventions for non-small cell lung cancer is radiotherapy. Ionizing radiation (IR) is classified by traditional radiobiology principles as a direct cytocidal therapeutic agent against cancer, although there is growing recognition of other antitumor immunological responses induced by this modality. The most effective therapeutic combinations to harness radiation-generated antitumor immunity and enhance treatment results for malignancies resistant to existing radiotherapy regimens could be determined by a more sophisticated understanding of the immunological pathways created by radiation...