The abscopal effect of immune-radiation therapy in recurrent and metastatic cervical cancer: a narrative review

Abstract

Despite human papillomavirus vaccination and screening, in about 5% of cases, cervical cancer (CC) is discovered at an initial metastatic stage. Moreover, nearly one-third of patients with locally advanced CC (LACC) will have a recurrence of their disease during follow-up. At the stage of recurrent or metastatic CC, there are very few treatment options. They are considered incurable with a very poor prognosis. For many years, the standard of care was the combination of platinum-based drug and paclitaxel with the possible addition of bevacizumab. The most recent years have seen the development of the use of immune checkpoint inhibitors (ICIs) (pembrolizumab, cemiplimab and others) in patients with CC. They have shown long term responses with improved overall survival of patients in 1st line (in addition to chemotherapy) or 2nd line (as monotherapy) treatment. Another emerging drug is tisotumab vedotin, an antibody-drug conjugate targeting tissue factor. Radiation therapy (RT) often has a limited palliative indication in metastatic cancers. However, it has been observed that RT can induce tumor shrinkage both in distant metastatic tumors beyond the radiation field and in primary irradiated tumors. This is a rarely observed phenomenon, called abscopal effect, which is thought to be related to the immune system and allows a tumor response throughout the body. It would be the activation of the immune system induced by the irradiation of cancer cells that would lead to a specific type of apoptosis, the immunogenic cell death. Today, there is a growing consensus that combining RT with ICIs may boost abscopal response or cure rates for various cancers. Here we will review the potential abscopal effect of immune-radiation therapy in metastatic cervical cancer.

Immune modulatory roles of radioimmunotherapy: biological principles and clinical prospects

“…In clinical practice, there are many factors affecting the abscopal effect of RT combined with ICIs, including radiation dose and segmentation, irradiation sites, general condition of patients, disease stage, tumor characteristics, the sequence of RT and ICIs, and the selection of different ICI agents ( 7 , 82 ). While radiation can activate the immune system, the optimal dose and timing of RT for the maximal abscopal effect is not fully understood ( 87 ).…”

“…Hence, the mechanisms of the abscopal effect explained in this study were as follows: After exposure to the systemic immune system of the immunogenic mutation induced by RT, tumor cells in the irradiated field were attacked by circulating immune cells and thus demonstrated distant anti-tumor responses. At present, the exact mechanism and principle of the abscopal effect of RT combined with ICIs observed in clinic remain unclear and warrant further investigations (82). In recent year, the abscopal effect of RT in combination with immunotherapy has attracted increasing attention from the public.…”

Progress in heavy ion cancer therapy at IMP and future development

“…In Table 3, it is interesting to note that a patient with fibrosarcoma of the upper arm was still with SD 6 months after treatment, but became CR 12 months after treatment. This anomaly may be caused by the immune responses triggered by radiation‐induced cancer cell death [17–27]. Rare but consistent reports regarding the abscopal effect of radiotherapy in cancer patients challenge the conventional notion of radioimmunology [17–27].…”

“…This anomaly may be caused by the immune responses triggered by radiation‐induced cancer cell death [17–27]. Rare but consistent reports regarding the abscopal effect of radiotherapy in cancer patients challenge the conventional notion of radioimmunology [17–27]. Radiation‐induced cancer cell death can trigger local/systemic immune responses against local/metastatic lesions [17–27].…”

STING agonist inflames the cervical cancer immune microenvironment and overcomes anti-PD-1 therapy resistance

“…Besides, the European Medicine Agency (EMA) approved Cemiplimab, a PD-1 specific antibody, in 2022 due to its significant enhancement in overall survival of cervical cancer (12.0 versus 8.5 months, HR = 0.69) ( 9 ). Ongoing clinical trials explore additional immunotherapies, signaling a potential paradigm shift in cervical cancer treatment by enhancing innate antitumor effects and reactivating the immune system ( 10 ).…”