Advancements in transplantation are inseparable from progress in immunomodulatory treatments. Since 1902, the advent of vascular suturing techniques has laid a crucial surgical foundation for organ transplantation. However, it was not until the 1970s, marked by the introduction of immunosuppressants such as tacrolimus and cyclosporine, that the challenge of transplant rejection was effectively addressed, facilitating the global expansion of clinical transplantation. Nevertheless, issues such as ischemia-reperfusion, which reshapes the immune microenvironment of the graft, refractory acute rejection, chronic rejection, de novo malignancies, and transplant infections remain critical clinical challenges that limit the long-term survival of recipients, with no satisfactory solutions currently available.

In recent years, immunotherapy has demonstrated remarkable efficacy in treating cancer and autoimmune disorders by modulating immune cell functions to either activate or suppress them, thereby achieving the elimination of tumor cells or the suppression of pathological immune responses. This class of drugs holds significant potential for addressing key challenges in transplantation. Numerous immunomodulatory treatments have been approved by the FDA for treating oncological and autoimmune diseases. The strategy of 'Drug Repurposing,' which accelerates the drug discovery process by identifying new clinical uses for existing drugs, allows for preclinical animal studies and clinical research on the effects of immunomodulatory treatments on transplant immune responses, providing new strategies for resolving critical issues in organ transplantation.

For instance, CTLA4 plays a significant role in T-cell immunity. CTLA4 inhibitors can activate T-cells in tumors, while CTLA4-Ig can suppress pathologically autoreactive T-cells. Both have been approved by the FDA for treating related diseases. Based on the strategy of drug repurposing, extensive research has confirmed the regulatory effect of CTLA4-Ig on alloimmune responses. Consequently, CTLA4-Ig was rapidly implemented in clinical practice within the field of transplantation medicine.

In summary, the integration of immunotherapy through drug repurposing, offers a promising avenue to overcome persistent barriers in transplantation. This approach not only enhances our understanding of immune mechanisms but also accelerates the application of effective treatments to improve patient outcomes.

The traditional pathway for drug discovery and development has yielded numerous essential medications that have significantly improved patient outcomes across various diseases. Nonetheless, a major challenge in this process is the frequent inability to secure drug approval and market authorization. Compared to oncology and autoimmune diseases, the field of transplantation faces unique challenges due to the significant impact of donor shortages, which substantially hinders the development of new drugs and limits therapeutic options in transplantation. To advance clinical practice in transplantation medicine, this Research Topic aims to explore the intersections and commonalities between immunological mechanisms in transplantation, cancer, and autoimmune diseases. Employing the strategy of 'drug repurposing,' we seek to uncover novel therapeutic approaches to address critical challenges in transplantation and enhance the efficiency of proposing new treatment strategies in this field.

This Research Topic invites submissions of Original Research, Clinical Trials, Systematic Reviews, Reviews, Mini-Reviews, Study Protocols, Case Reports, and Brief Research Reports. We encourage manuscripts that focus on, but are not limited to, the following sub-topics:

• Clinical trials within transplantation cohorts employing the 'drug repurposing' strategy, including meta-analyses, systematic reviews, and study protocols related to such trials, as well as case reports on rare transplantation cases treated with repurposed drugs.

• Reviews and mini-reviews discussing therapeutic methods in transplantation that hold potential for 'drug repurposing'.

• Original research using bioinformatics approaches to identify drugs within the transplantation field that are candidates for 'drug repurposing'.

• Original and brief research studies using animal models, cellular biology, and molecular biology techniques to examine the effects of oncological and autoimmune drugs with potential for 'drug repurposing' on critical events in transplantation such as ischemia-reperfusion injury, T-cell mediated rejection, donor-specific antibody (DSA) formation, and chronic rejection and et al.

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Frontiers in Immunology

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