64 Immunosurveillance, the immune system’s natural ability to detect and eliminate cancer cells, has become a cornerstone in contemporary cancer management. A recent study published in CA: A Cancer Journal for Clinicians explores the implications of immunosurveillance in clinical cancer management, underscoring its critical role in enhancing the effectiveness of various cancer therapies. Immunosurveillance refers to the immune system’s ability to recognise and destroy emerging tumour cells, thereby preventing cancer development. This process involves various immune cells, including T lymphocytes and natural killer cells, which identify and eliminate abnormal cells. However, for cancer to progress, malignant cells must evade or suppress this immune response, leading to tumour growth and metastasis. The study highlights that the effectiveness of many anticancer treatments, including chemotherapy, radiation therapy, and targeted therapies, is significantly enhanced when these treatments restore or enhance immunosurveillance. This is especially clear with immunotherapies like immune checkpoint inhibitors (ICIs), which have changed the way cancer is treated by turning on the immune system again to fight cancer cells. ICIs work by blocking inhibitory pathways that suppress immune activity, thereby allowing T cells to attack cancer cells more effectively. The combination of ICIs with other treatments, such as chemotherapy or radiation, can induce a state known as immunogenic cell death, where dying cancer cells release signals that further stimulate the immune response. The study discusses several combinatorial strategies that have shown promise in clinical settings. For example, combining ICIs with conventional chemotherapy has resulted in improved outcomes for patients with various cancers, including melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer. Neoadjuvant (pre-surgical) chemoimmunotherapy has higher rates of complete pathological responses in NSCLC than chemotherapy alone. This means that patients do not need as much surgery and have a better chance of survival. The study also shows that neoadjuvant ICIs that target PD-1 have made a lot of progress against different types of cancer, either by themselves or in combination with other ICIs or chemotherapy. These combinations have shown high rates of profound pathological responses, reduced surgical interventions, and shorter treatment durations. Despite these advancements, several challenges remain. One significant issue is the severe side effects associated with combinatorial strategies involving multiple ICIs. These side effects can be more severe than those observed with single-agent treatments, highlighting the need for careful patient selection and management. The study also emphasises the importance of biomarkers in predicting and monitoring the response to treatment. To find patients who are likely to benefit from ICIs, biomarkers like PD-L1 expression, tumour mutation burden, and microsatellite instability are very important. Additionally, understanding the tumour microenvironment and the body’s systemic immune responses can help personalise treatments and improve outcomes. The future of cancer treatment appears to be moving towards more personalised and precise approaches, incorporating immunotherapy at earlier stages of the disease. Neoadjuvant immunotherapy is very promising because it can move immune responses against tumours into the most effective phase of immunosurveillance. This could mean that extensive surgery and adjuvant therapies are not needed after all. The study suggests that developing new combinatorial treatments that consider both local and systemic immune effects will be crucial. This includes exploring the role of the microbiota, systemic metabolism, and other bodywide ecological factors that impact immunosurveillance and therapeutic responses.