Neoadjuvant chemoradiotherapy (nCRT) is recommended for the treatment of locally advanced rectal cancer. Even though the combination of nCRT and immune checkpoint inhibitors (ICIs) has received much attention, the specific combination modes and dose fractions in radiotherapy (RT) are still indistinct. This review focuses on the immunological mechanism involved in nCRT, the clinical efficacy, the immunological effect of different combined strategies, concurrent or sequential nCRT plus ICIs, long-course RT and short-course RT. This review discusses the impact of nCRT on tumor immunity and summarizes the availability of different dose fractions in RT and distinct combined strategies, aiming at providing clues for optimal neoadjuvant therapy options that maximize efficacy and minimize side effects.
Keywords: dose fractionation; immune checkpoint inhibitors; immune microenvironment; locally advanced rectal cancer; neoadjuvant chemoradiotherapy.
Radiotherapy (RT) and/or chemotherapy before surgery is the most common therapeutic strategy for patients with rectal cancer. This review summarizes the changes in tumor immunity, including immune cells and immune components, after receiving RT and chemotherapy. The authors looked for clues to the proper strategy of combined RT, chemotherapy and other novel agents to magnify antitumor immunity based on these changes. In addition, it emphasizes the RT regimens implicated in distinct immune alterations, which might help improve the efficacy of RT in clinical applications.