Natural Killer (NK) cells are innate immune cells known for their ability to recognize and destroy tumor cells without prior sensitization. NK cells are distinguished from other immune cells by their ability to target cells that lack MHC class I molecules, which are often downregulated in tumor cells as a mechanism to evade T cell-mediated immunity. NK cells express a range of activating and inhibitory receptors that regulate their function, making them crucial in the immune surveillance against cancer. TILs, particularly CD8+ cytotoxic T cells, recognize tumor-associated antigens presented by MHC class I molecules on the surface of cancer cells. This recognition leads to the activation and killing of the tumor cells. TILs secrete various cytokines, such as IFN-γ and TNF-α, which help in orchestrating a broader anti-tumor immune response and modifying the TME to make it less conducive to tumor growth. TILs can develop into memory T cells, providing long-term surveillance against tumor recurrence. Both NK cells and TILs play crucial roles in anti-tumor immunity, and combining these approaches could potentially synergistically enhance therapeutic outcomes. For example, NK cells can modulate the TME and facilitate T cell infiltration, while TILs can provide targeted adaptive immune responses. The combination of NK cell-based therapies with TIL therapies or checkpoint inhibitors represents a promising avenue for developing more effective cancer treatments. • GPC3 | CAR-T Glypican-3 (GPC3) is a cell surface proteoglycan that is part of the glypican family, involved in cell growth, differentiation, and migration. GPC3 is highly expressed in several cancers, most notably HCC, but is absent or minimally expressed in normal adult tissues, making it an attractive target for cancer immunotherapy. GPC3 is involved in the regulation of cell signaling pathways, such as Wnt/β-catenin, which are critical for tumor growth and development. Overexpression of GPC3 is associated with increased tumor proliferation and poor prognosis in cancers like HCC. The restricted expression of GPC3 to tumor cells, particularly in HCC, but not in most normal tissues, makes it an ideal target for immunotherapies that aim to minimize off-target effects. For GPC3, CAR-T cells are engineered to target GPC3-expressing tumor cells, especially in cancers like hepatocellular carcinoma. 366-368 GPC3-targeted CAR-T therapies are being evaluated in clinical trials, particularly for the treatment of HCC. Innovations such as dual-targeting CAR-T cells (which target GPC3 and another tumor antigen), armored CAR-T cells (engineered to secrete cytokines or express checkpoint inhibitors), and combination therapies are being explored to enhance the therapeutic potential of GPC3-targeted CAR-T cells. GPC3 is a promising target in immuno-oncology due to its tumor-specific expression and role in tumorigenesis. CAR-T cell therapy targeting GPC3 offers a powerful approach to treating cancers like HCC. While challenges remain, ongoing research and clinical trials continue to refine these therapies, with the goal of improving outcomes for patients with GPC3-positive cancers. • ROS | photothermal therapy (PTT)