International Journal of Clinical Case Reports 2024, Vol.14, No.4, 189-201 http://medscipublisher.com/index.php/ijccr 197 immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), which inhibit effective anti-tumor immune responses (Álvarez Ballesteros et al., 2021). Targeting the TME, particularly through inhibiting pathways like PI3Kγ in myeloid cells, has shown promise in reversing resistance and enhancing the efficacy of ICIs. Additionally, combination therapies that pair ICIs with agents targeting angiogenesis, such as VEGF inhibitors, or novel immunomodulatory agents are being explored to overcome immune resistance and extend patient survival (Moreira et al., 2020). Future strategies will likely focus on a precision medicine approach, tailoring treatments based on the specific mechanisms driving resistance in individual patients. 6.2 Novel immunotherapeutic strategies In addition to checkpoint inhibitors, novel immunotherapeutic strategies, such as bispecific antibodies and chimeric antigen receptor T (CAR-T) cell therapy, are emerging as promising treatments for RCC. Bispecific antibodies (BsAbs), such as bispecific T-cell engagers (BiTEs), are designed to engage both T cells and tumor cells by simultaneously binding to a tumor antigen and a T-cell receptor, thereby directing the immune system to target cancer cells more effectively. While BsAbs have shown significant efficacy in hematologic malignancies, their success in solid tumors like RCC has been limited, largely due to the immunosuppressive TME (Goebeler and Bargou, 2020). Research is ongoing to improve their effectiveness by combining BsAbs with other immunotherapies or modifying their structure to enhance their function in solid tumors (Zhou, 2024). CAR-T cell therapy, which involves engineering a patient’s T cells to express receptors specific to tumor antigens, has been revolutionary in treating certain blood cancers. However, its application in solid tumors, including RCC, has faced challenges related to the TME and the difficulty of targeting appropriate antigens. Efforts are being made to modify CAR-T cells to enhance their persistence and efficacy in the hostile environment of solid tumors. For instance, using CAR-T cells that secrete pro-inflammatory cytokines or combining them with checkpoint inhibitors may improve outcomes in RCC patients (Figure 2) (Martínez-Sabadell et al., 2022). As research advances, these therapies hold potential for transforming the treatment landscape for RCC. 6.3 Prospects for personalized immunotherapy The future of cancer treatment is increasingly moving toward personalized immunotherapy, where treatment is tailored to the unique characteristics of each patient’s tumor and immune profile. Advances in genomic sequencing, immunoprofiling, and liquid biopsies have enabled the identification of predictive biomarkers, such as tumor mutational burden (TMB), microsatellite instability (MSI), and specific genetic mutations (e.g., in PBRM1 or JAK2), which can help predict a patient's response to immunotherapy (Meng et al., 2023). This allows clinicians to select the most effective therapies for each patient, minimizing unnecessary treatments and improving outcomes. Moreover, the development of novel immunotherapies, such as personalized cancer vaccines, oncolytic viruses, and adoptive T-cell therapies, offers the potential for more precise targeting of tumors based on their immunogenic characteristics. For example, therapeutic cancer vaccines aim to stimulate the patient’s immune system to recognize and attack tumor-specific antigens, while oncolytic viruses can selectively infect and kill cancer cells while boosting immune responses. By integrating these novel approaches with existing ICB therapies, personalized immunotherapy could significantly improve survival rates and quality of life for RCC patients (Moreira et al., 2020). As the field of immuno-oncology evolves, the goal is to develop more individualized treatment plans that take into account not only the genetic makeup of the tumor but also the patient's overall immune health and response to therapy. This approach is expected to enhance the effectiveness of immunotherapies and reduce treatment-related toxicities, leading to better patient outcomes in the future.
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