Cancer Genetics and Epigenetics, 2025, Vol.13, No.6, 300-309 http://medscipublisher.com/index.php/cge 302 that whether used alone or in combination with chemotherapy, the overall survival rate can be significantly improved, especially for patients with higher PD-L1 expression (Gandhi et al., 2018). Furthermore, nivolumab and atezolizumab have continuously demonstrated stable efficacy and survival benefits in both newly diagnosed and multi-line treated patients. In the treatment of advanced melanoma, ICIs that act on PD-1 (such as nivolumab, pembrolizumab) and CTLA-4 (such as ipilimumab) have become commonly used regimens. The long-term follow-up results of the CheckMate 067 study indicated that the combination therapy of nivolumab and ipilimumab brought unprecedented 5-year survival data. More than half of the patients were still alive after 5 years, which was a significant improvement compared with previous treatment methods (Larkin et al., 2019). These achievements demonstrate that ICIs has profound value in the treatment of melanoma. Some patients can maintain good therapeutic effects even after discontinuing treatment. 3.2 Progress in key research on renal cell carcinoma and digestive tract tumors In renal cell carcinoma (RCC), ICIs has become an important component of first-line treatment. The CheckMate 214 trial demonstrated that for patients with moderate to low risk advanced renal cell carcinoma, the combination of nivolumab and ipilimumab was more effective than sunitinib, and both overall survival and tumor response rates of patients were improved (Motzer et al., 2018). In recent years, the combination regimen of ICIs and anti-angiogenic targeted drugs (such as pembrolizumab combined with axitinib) has further improved the therapeutic effect. The results of the KEYNOTE-426 trial showed that this regimen had more advantages than sunitinib in terms of survival and response rate (Figure 1) (Rini et al., 2019). The effect of ICIs in digestive tract tumors varies depending on the type of cancer, but significant progress has been made in some patients. In metastatic colorectal cancer, pembrolizumab and nawolumab have demonstrated outstanding performance in patients with MSI-H or dMMR characteristics, achieving a high response rate and maintaining a long therapeutic effect. Therefore, they have been approved by the FDA for this population. In the treatment of gastric cancer and esophageal cancer, studies such as KEYKEYNOTE 059 and ATTRACTION 2 have shown that pembrolizumab and nivolumab can also bring survival advantages in PD-L1-positive or previously treated patients (Fuchs et al., 2018). 3.3 Preliminary results and future applications in breast cancer, gynecological tumors and other solid tumors ICIs have shown certain potential in breast cancer, especially triple-negative breast cancer (TNBC), but research is still ongoing. The IMpassion130 trial demonstrated that the combination of NAB-paclitaxel and atezolizumab could prolong the progression-free survival of patients with PD-L1-positive metastatic triple-negative breast cancer. Therefore, this regimen was approved for such patients (Schmid et al., 2018). However, subsequent studies have suggested that more effective biomarkers and combination treatment strategies need to be sought to expand the beneficiary population (Adams et al., 2019). In terms of gynecological tumors, ICIs is effective for certain types of endometrial cancer and cervical cancer, especially for those patients with MSI-H/dMMR characteristics or high expression of PD-L1. Pembrolizumab has been approved for the treatment of PD-L1-positive recurrent or metastatic cervical cancer, as well as MSI-H/ DMMR-related endometrial cancer (Chung et al., 2019). Research on ovarian cancer and other solid tumors is still advancing. Early results show that it is effective in patients with certain specific molecular or immune characteristics, suggesting that ICIs may be applicable to more patients in the future. 4 Main Factors Affecting the Efficacy of Immunotherapy 4.1 Biomarkers: PD-L1 expression, number of tumor mutations (TMB), and MSI/dMMR status Finding biomarkers that can predict the efficacy of immune checkpoint inhibitors (ICIs) is of great significance for improving the therapeutic effect of solid tumors. The expression of PD-L1 on tumor or immune cells is a commonly used marker at present. In cancers such as non-small cell lung cancer and melanoma, patients with higher PD-L1 levels usually have a better response to PD-1/PD-L1 inhibitors. However, PD-L1 is not a perfect
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