International Journal of Clinical Case Reports 2024, Vol.14, No.4, 189-201 http://medscipublisher.com/index.php/ijccr 198 Figure 2 IFN-γ response is required for efficient killing by redirected lymphocytes (Adopted from Martínez-Sabadell et al., 2022) Image caption: The response of target cells to HER2-TCB and HER2-CAR T cells in the presence or blockade of IFN-γ. Blocking IFN-γ significantly reduced the killing efficacy of these immunotherapies, indicating that IFN-γ is crucial for eliciting maximum T-cell anti-tumor activity. This further confirms that IFN- γ is indispensable for effective immunotherapy (Adapted from Martínez-Sabadell et al., 2022). 7 Concluding Remarks Immune checkpoint blockade (ICB) therapy has significantly transformed the treatment landscape for renal cell carcinoma (RCC). However, numerous challenges remain, particularly regarding resistance to therapy and optimizing treatment regimens. This concluding section will summarize the efficacy of ICB in RCC and discuss the implications for future research and clinical practice. ICB therapies, particularly those targeting PD-1, PD-L1, and CTLA-4, have demonstrated significant clinical benefits in RCC patients, especially in the metastatic setting. Agents such as nivolumab and pembrolizumab have shown improved survival outcomes, including longer progression-free survival (PFS) and overall survival (OS) compared to traditional therapies. In particular, combination therapies like nivolumab and ipilimumab or pembrolizumab with tyrosine kinase inhibitors (TKIs) have resulted in higher response rates and longer-lasting remissions for many patients. Clinical trials like CheckMate 214 and KEYNOTE-426 have established these combination regimens as standard treatments in metastatic RCC, with evidence showing improved OS and objective response rates (ORR) compared to sunitinib monotherapy. However, while these treatments have provided new hope, only a subset of patients experience durable responses, and resistance to therapy remains a key challenge. Looking forward, overcoming immune resistance is one of the most critical challenges in ICB therapy for RCC. Future research must focus on better understanding the mechanisms driving both primary and acquired resistance, including the role of the tumor microenvironment and immune evasion tactics employed by cancer cells. Targeting myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and exploring epigenetic modulators like HDAC inhibitors could offer new avenues to improve ICB efficacy. Another area ripe for exploration is the development of novel immunotherapies such as bispecific antibodies and CAR-T cells, which could enhance the targeting of cancer cells in patients who do not respond to traditional ICBs. Moreover,
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