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Advances in Radiotherapy
& Nuclear Medicine Advancements and challenges in radioactive iodine-125

occurred. Specifically, the majority of these cells were of brachytherapy with PD-1/PD-L1 blockade therapy for
Th1 subtype, while only a small proportion represented prostate cancer could be particularly effective [80,81] .
prostate cancer-specific Th2 and Th17 subtypes. Th1 cells, A recurring observation across these studies involves
the main subtype of CD4+ T cells, play a pivotal role in the detection of potential remote immune activation
the tumor immune response . They accomplish this by through peripheral blood analysis, situated away from
[74]
secreting cytokines such as IFN-γ and tumor necrosis the primary tumor. In addition, these investigations have
factor-α, which have the ability to eliminate tumor cells further identified compensatory immune suppression
and, consequently, contribute to anti-tumor immune signals following brachytherapy. This suppression
responses . T-bet, a characteristic transcription factor manifests in various forms, including the upregulation
[75]
located on the surface of Th1 cells, is responsible for of Tregs and the activation of well-established immune
regulating their differentiation, maturation, and the checkpoints such as PD-L1. The emergence of immune
[76]
secretion of these cytokines . suppression subsequent to radiation exposure has
A study investigated the changes in the distribution previously been described in the context of in vitro beam
of tumor-infiltrating T lymphocytes in prostate cancer radiation. This phenomenon may also constitute a limiting
patients, both before and after radical prostatectomy, factor within the realm of I-125 brachytherapy. Overall,
particularly focusing on cases of biochemical recurrence. these data lend support to the notion of combining I-125
The findings revealed a substantial increase in the brachytherapy with immunotherapy. Such a combination
infiltration of CD8+, PD-1+, and Foxp3+ T cells compared holds the potential not only to improve localized tumor
to pre-surgery levels when biochemical recurrence was elimination but also to enhance distant anti-tumor
observed. Among these, Treg cells, an important subset of immune responses.
CD4+ T lymphocytes known for their immunosuppressive
activity, play a significant role in inhibiting the anti-tumor 6. Discussion and perspective
immune response . The transcription factor Foxp3 is Reflecting on the evolution of interstitial I-125
[76]
specific to Treg cells and regulates their differentiation brachytherapy, the pursuit of precision in brachytherapy
and maturation . Furthermore, it was observed that has consistently remained a common goal of medical
[77]
the increased presence of PD-1+ and Foxp3+ T cells was professionals and scholars in this field. As imaging
negatively correlated with patient prognosis. The study technology has continuously advanced, it has provided
suggested that this phenomenon may be attributed to clinicians with a visual “eye,” progressively expanding
genetic mutations occurring during tumor relapse, which the scope of applications for I-125 brachytherapy.
result in the induction of new tumor antigens and a Concurrently, the continuous optimization of this “vision”
subsequent immune response. The increased expression of has enhanced the accuracy of I-125 brachytherapy.
PD-1+ T cells in the tumor after the activation of tumor- On the one hand, the development of I-125
specific T lymphocytes is considered a manifestation of brachytherapy has been dose-oriented, focusing on
immune escape .
[78]
achieving greater accuracy in irradiation dosage delivery.
After prostate cancer brachytherapy, the This dedication to enhancing accuracy has been exemplified
immunostimulatory effect on the tumor diminishes as by the introduction of 3D-printed personalized templates,
the radioactivity of implanted particles decreases. While a treatment planning systems, and robot-assisted systems.
substantial number of CD4+ and CD8+ T cells continue These innovations collectively contribute to a more
to infiltrate the tumor, the expression of PD-1+ T cells accurate dose delivery. Predicting future developments,
remains low, indicating a reduction in the presence of including new products, their potential applications, and
tumor antigen-specific T cells. Moreover, in alignment with the challenges they may introduce, poses a considerable
the concept of tumor immune editing, it was observed that challenge. Therefore, the competence of medical physicists
as prostate cancer relapses and progresses, the expression becomes increasingly vital when it comes to the clinical
of PD-1+ T cells gradually decreases, indicating a gradual implementation and evaluation of innovative brachytherapy
weakening of the tumor-specific immune response. This devices and applications. The sensitivity of various tumor
phenomenon aligns with the characteristics of tumor tissues to radiotherapy in I-125 brachytherapy varies.
immune evasion . In light of these observations, it is However, apart from prostate cancer, determining the
[79]
postulated that the immune microenvironment within optimal radiation dose for other tumors remains an
prostate cancer tumors undergoes dynamic changes ongoing challenge. While there have been several editions
following I-125 brachytherapy. This suggests the existence of consensus proposing recommended dose ranges for
of a specific time frame during which combining I-125 different tumor types, many of these recommendations

Volume 1 Issue 2 (2023) 8 https://doi.org/10.36922/arnm.0914