Analysis of TCR modification and tumor microenvironment associated with radiation therapy for cervical cancer and development of new treatment modalities

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18213
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: The University of Tokyo
• Principal Investigator: YOSHIDA MITSUYO 東京大学, 医学部附属病院, 届出研究員 (10833618)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 子宮頸癌 / 放射線療法 / 腫瘍内微小環境 / TCR改変

Outline of Final Research Achievements

The standard therapy for locally advanced cervical cancer is chemoradiation. Radiation therapy induces changes associated with the induction of inflammatory cytokines as well as cellular injury. Therefore, it is important to consider local and systemic immunity in predicting the therapeutic effect of radiotherapy. In this study, we aimed to predict the therapeutic effect of radiotherapy for cervical cancer by focusing on inflammation and immune response. We used machine learning to predict prognosis based on clinicopathological features, MRI images, and blood data from 262 patients who had undergone radiation therapy for cervical cancer. As a result, tumor diameter, SCC value, and histological type were extracted as prognostic predictors. Focusing on inflammation and immune markers, neutrophil count was found to be an important prognostic factor.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

子宮頸癌ではhuman papilloma virus (HPV)の感染が、発癌や癌の進展と関わっている。ウイルス感染に伴う「宿主の免疫応答」と、「ウイルスの宿主免疫からの回避」のバランスにより、持続感染や発癌が制御されている。子宮頸癌の治療方法は、進行子宮頸癌に対しては化学放射線療法が選択されることが多いが、進行子宮頸癌の5年生存率は50%程度であり、十分とは言い難い。本研究では、炎症や免疫応答に着目して、子宮頸癌の全身性免疫や局所免疫を評価することで、治療効果を予測した。さらに、放射線療法後に出現もしくは増加するT細胞を同定することでより強力な細胞療法の候補を選定することも目的とした。