Radiation therapy is widely used in cancer treatment[1], [2]. Its mechanism is to destroy the DNA of cancer cells through ionizing radiation to kill cancer cells and prevent the growth and spread of cancer cells[3]. Radiation therapy can also be used in conjunction with other treatments[4], [5], [6], [7] such as surgery and chemotherapy to increase the effectiveness of the treatment[8]. Radiation therapy can be used to kill cancer cells through different types of radiation, such as X-rays[9], gamma rays[10], and proton beams[11], [12], [13]. During treatment, radiation can be directed to the tumor site in the patient's body in conjunction with medical imaging to minimize damage to healthy tissue. Radiation therapy, as an effective cancer treatment, has some drawbacks and risks[2]. Radiation therapy not only kills cancer cells but also causes some damage to the surrounding healthy tissues and may cause discomfort and side effects such as skin inflammation, fatigue, nausea, and vomiting[14]. And it may cause some long-term side effects such as decreased heart and lung function, osteoporosis, cataracts, and neurological damage[15], [16]. There is also a risk that it may not completely kill all the cancer cells and cause the cancer to recur. As radiation therapy requires multiple exposures, the treatment process may be lengthy and requires patience and cooperation from the patient. Some types of cancer cells are not sensitive to radiation therapy, so it may be necessary to combine them with other treatments, such as chemotherapy and surgery[17].

Immunotherapy represents a paradigm shift in disease management, particularly in oncology, leveraging the inherent capabilities of an individual's immune system. This therapeutic approach harnesses and augments the immune response, enabling a targeted assault on malignant cells[18]. Central to immunotherapy is the premise of immune system manipulation—bolstering its ability to identify and eradicate cancerous cells[19]. Typically, the immune system adeptly detects and neutralizes foreign entities and aberrant cells, including pathogens and neoplastic cells. Yet, cancer cells often deploy evasive strategies, circumventing immunological detection and subsequent destruction[20], [21]. The strategic objective of immunotherapy lies in its capacity to recalibrate and fortify the immune response, thus reinstating its inherent cancer cell recognition and annihilation functions. This intervention operates on the principles of immunological specificity and memory, equipping the immune system with an enhanced ability to discern and combat cancer cells, thereby offering a therapeutic pathway[22]. Immunotherapy's modalities range from stimulating the immune system's intrinsic defenses to more intricate approaches involving synthetic analogs of immune components. This versatility positions immunotherapy as a formidable alternative or adjunct to conventional modalities like chemotherapy and radiotherapy[23]. It offers distinct advantages in terms of specificity, durability of response, and a reduced spectrum of adverse effects, minimizing collateral damage to healthy tissue. Furthermore, immunotherapy uniquely primes the immune system for long-term vigilance, potentially curbing cancer recurrence and metastasis[24], [25]. Despite notable successes, particularly in specific cancer subtypes, immunotherapy's efficacy varies. Its performance is often enhanced when integrated with other treatment modalities. This variability underscores the necessity for continued research into the mechanistic underpinnings and potential synergies of immunotherapy, both as a standalone and in combination regimens. Such investigations are imperative to optimize clinical application, offering more efficacious and personalized therapeutic avenues for cancer patients.

The interaction between radiation therapy and immunotherapy in cancer treatment presents a multifaceted landscape, marked by both synergistic and antagonistic effects. Studies suggest that in certain scenarios, a combination of radiation and immunotherapy may surpass the efficacy of either modality employed independently[26], [27]. Radiation therapy can act as an immune system stimulant by inducing an inflammatory milieu within the tumor microenvironment[28]. This can be exemplified by the abscopal effect, where radiation therapy not only impacts the targeted tumor site but also facilitates a broader immune-mediated attack on distant tumor cells[29]. However, the influence of radiation on immunotherapy is dual-faceted [30]. While it can potentiate the immune response, radiation can concurrently exert immunosuppressive effects[31], [32], potentially hindering the effectiveness of immunotherapeutic agents. This duality necessitates a nuanced understanding of the interplay between these treatments. Additionally, the combined use of radiation and immunotherapy may exacerbate side effects compared to when these treatments are applied separately. The temporal sequence and scheduling of radiation and immunotherapy are critical determinants of their interdependent effectiveness. Administering radiation before immunotherapy can catalyze an inflammatory response, potentially amplifying the immunotherapeutic effect. Conversely, radiation following immunotherapy could dampen the immune response, diminishing the overall therapeutic impact. Ultimately, the interaction between radiation and immunotherapy is intricate and influenced by multiple variables, including the cancer type, the specific immunotherapeutic agents used, and the strategic timing and sequencing of the treatments. This complexity underscores the necessity for personalized treatment planning and further research to optimize these combined therapeutic strategies.