Core Viewpoint - The article discusses the promising potential of PD-1 and PD-L1 blockade in cancer treatment, particularly highlighting the challenges faced in treating mismatch repair proficient (pMMR) colorectal cancer (CRC), which constitutes over 95% of CRC patients and is characterized as "cold tumors" that do not respond to PD-1/PD-L1 therapies due to immune suppression in the tumor microenvironment [3][4]. Group 1 - The combination of molecular targeted approaches to release damage-associated molecular patterns (DAMPs) with immune checkpoint inhibitors (ICIs) shows good prospects for treating pMMR CRC [4]. - A novel peptide-grafted polymer-based nanorobot has been developed that can block PD-1/PD-L1 while simultaneously inducing immunogenic cell death (ICD) by disrupting cancer cell membranes, thereby enhancing T cell infiltration [5][7]. - This nanorobot exhibits high specificity by targeting PD-L1 overexpressing cancer cells, ensuring prolonged retention in tumors (> 120 hours) and activating T cell responses against the tumor [7][8]. Group 2 - The nanorobot not only transforms "cold tumors" into "hot tumors" by releasing the inhibition on immune cells but also actively generates inflammatory signals to recruit immune cells, achieving a synergistic effect that enhances therapeutic efficacy [8]. - In preclinical models, this nanorobot demonstrated superior therapeutic effects compared to traditional treatments combining anti-PD-L1 antibodies and oxaliplatin, indicating its significant potential for clinical application in colorectal cancer immunotherapy [10].