Cancer treatment and research最新文献

Artificial intelligence (AI) and machine learning (ML) are revolutionizing cancer immunotherapy by addressing the complex interplay between cancer and the immune system. This chapter explores how AI technologies enhance immunotherapy development across multiple domains: antibody design, response prediction, biomarker identification, and T-cell target discovery. In therapeutic antibody design, AI improves efficiency through predictive modeling of antibody-antigen interactions, structure prediction tools, generative models that create novel antibody sequences, and developability optimization. Clinical applications include AI-powered systems that predict immunotherapy responses using multi-omics data integration, helping distinguish pseudoprogression from true disease progression. Beyond conventional biomarkers like programmed cell death protein 1, AI enables identification of additional markers including tumor mutational burden, microsatellite instability, immune cell infiltration patterns, and novel genomic alterations. Multi-omics approaches leverage AI to synthesize diverse data types, uncovering complex biomarker signatures that more accurately predict treatment outcomes. For T-cell target identification, next-generation immunoediting platforms like Gritstone's EDGE™ system exemplify AI-powered approaches that precisely identify neoantigens by integrating sequencing technologies with sophisticated prediction algorithms (Table 2.1). These platforms support both personalized and shared antigen approaches to immunotherapy, potentially enhanced through integration with innate immune pathways. Despite remarkable progress, challenges persist in addressing tumor heterogeneity, immune evasion mechanisms, and technical limitations in prediction algorithms. The continued refinement of AI approaches, expansion to diverse cancer types, and integration with complementary therapeutic modalities represent promising future directions. Overall, AI and ML are poised to transform cancer immunotherapy by enabling more precise, effective, and personalized treatment approaches that harness the immune system's power against cancer.

Cancer immunotherapy is a major advancement in the field. It works by stimulating the patient's immune system to recognize and destroy cancer cells. Several different types of cancer immunotherapies have been developed, such as T-cell therapy, immune checkpoint inhibitors, monoclonal antibodies, cancer vaccines, and many others, which can result in sustainable responses in patients with a wide range of metastatic diseases. Additionally, immunotherapy drugs are being combined with chemotherapy and other targeted therapies to treat a variety of cancer types. Despite the promising results, several challenges remain, such as the almost inevitable immune resistance, drug-related toxicity, and the lack of established and reliable predictive biomarkers to predict toxicity and/or discern a patient's response to immunotherapy. In this chapter, we summarize the mechanisms underlying cancer immunotherapy resistance, especially the contributions of phenotypic plasticity and the underlying non-genetic mechanisms. Furthermore, recent developments in preventing relapses following treatment so that the efficacy of immunotherapy can be improved are also briefly discussed. Finally, the positive impact of an interdisciplinary "Team Medicine" approach to personalize cancer immunotherapy for each patient is highlighted.

Colorectal cancer (CRC) is a growing concern worldwide, particularly affecting younger populations in recent years. The progression of CRC involves diverse molecular pathways, each contributing to how the tumor behaves and responds to treatment. The immune system is crucial in detecting and destroying cancer cells, but tumors can avoid immune destruction through various strategies, such as altering antigen expression or reshaping their environment to suppress immune activity. These escape mechanisms have prompted the development of immunotherapy, which has significantly improved outcomes for patients with specific genetic profiles like microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). Drugs such as pembrolizumab, nivolumab, and others have demonstrated notable clinical benefits in these populations. Research is now expanding to evaluate immunotherapy in earlier stages of disease and in combination with other treatments like chemoradiation, even in patients without traditional predictive biomarkers. Ongoing studies are also exploring novel immune targets and combinations to enhance effectiveness and broaden access to these therapies. Understanding the interaction between tumor biology and the immune system is essential for advancing personalized care in CRC.

There have been tremendous advancements in immunotherapy approaches for patients with renal cell carcinoma (RCC) from the initial interleukin-2 era to the current immune checkpoint inhibitor (ICI) combinations. Several ICI-based therapies have greatly improved outcomes for patients with RCC with the potential for durable responses for a subset of patients. In this chapter, we review the data of key frontline ICI-based combinations for RCC in the metastatic setting and recent data on adjuvant immunotherapy. We also discuss recent data on the role of immunotherapy rechallenge following prior ICI treatment as well as emerging novel immunotherapy strategies with chimeric antigen receptor (CAR) T and gut microbiome interventions. Lastly, we highlight a multidisciplinary team-based approach for patients with RCC treated with ICI including management of immune-related adverse events as well as potential role of cytoreductive nephrectomy in an evolving treatment landscape.

This chapter explores systemic treatment strategies for cutaneous melanoma across neoadjuvant, adjuvant, and Stage IV settings. Neoadjuvant therapy aims to reduce tumor burden pre-surgery, primarily using immune checkpoint inhibitors like nivolumab plus ipilimumab, showing promising response rates. Adjuvant therapy, post-resection, leverages immunotherapy (e.g., nivolumab) and targeted therapies (e.g., dabrafenib plus trametinib) to prevent recurrence in high-risk patients, improving relapse-free survival. Stage IV systemic treatment addresses metastatic disease, employing immunotherapy (nivolumab, pembrolizumab) and targeted mitogen-activated protein kinase (MAPK) pathway inhibitors (dabrafenib plus trametinib) for BRAF-mutant cases, while BRAF wild-type patients benefit from nivolumab-relatlimab or combination therapies. Tables summarize key regimens, efficacy, and toxicities. Content aligns with clinical guidelines, with updates on emerging therapies like tumor-infiltrating lymphocytes (TIL). These approaches enhance survival and treatment-free intervals, tailored to mutation status and disease stage.

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) makes up the large majority of lung cancer diagnoses. After the discovery of immune modulators or immunotherapy, treatments that could utilize the patient's own immune system to target malignant cells, the landscape of lung cancer treatment, NSCLC in particular, has greatly evolved with vast improvements in outcomes and survival. Currently, immune checkpoint inhibitors (ICI) have had the greatest impact on the current treatment of non-driver mutated non-small cell lung cancer. Unfortunately, resistance to treatment whether primary or secondary, remains a concern. To overcome resistance, investigators have sought combination immune modulator treatments and have even identified novel agents to utilize, including adoptive cellular therapies, antibody-drug conjugates, and vaccines. Some of these agents have been more successful than others with combination strategies currently leading the way but there are some limitations. Other agents are early in development and will need to await further data before determining the impact on lung cancer treatment. Immunotherapy or immune modulatory agents remain an essential aspect of NSCLC treatment and continue to be the subject of novel research and development.

Immunotherapy has reshaped the treatment landscape of several malignancies, including breast cancer. While historically considered less immunogenic, breast cancer-particularly the triple-negative subtype (TNBC)-has demonstrated responsiveness to immune checkpoint inhibitors (ICIs). TNBC is characterized by higher tumor mutational burden, elevated PD-L1 expression, and increased tumor-infiltrating lymphocytes, making it a leading focus of immunotherapy development. In metastatic TNBC with PD-L1 expression, trials such as KEYNOTE-355 have shown improvements in progression-free and overall survival with the addition of the ICI, pembrolizumab to chemotherapy, leading to regulatory approval. In early-stage TNBC, KEYNOTE-522 established a neoadjuvant chemotherapy plus ICI as the standard of care for stage II and III tumors. This was based on improved pathologic complete response and event-free survival in this pivotal clinical trial regardless of PD-L1 expression. ICIs in other subtypes, such as HER2-positive and hormone receptor-positive/HER2-negative disease, remain under active investigation. Ongoing studies are also exploring novel strategies including dual immune checkpoint blockade, cellular therapies (e.g., CAR-T, TILs), cancer vaccines, and rational combinations with targeted agents and antibody-drug conjugates (ADCs). Biomarkers such as PD-L1, tumor mutational burden, immune gene signatures, and the gut microbiome are being evaluated to refine patient selection and predict response. Additionally, effective management of immune-related toxicities is critical, particularly in curative-intent settings. As the role of immunotherapy expands, a multidisciplinary, biomarker-driven approach will be essential to optimize outcomes and broaden its applicability across breast cancer subtypes.

Immunotherapy has had a profound impact on how we treat cancer. Immunotherapy takes advantage of the body's immune system to combat the disease and is considered as one of the pillars of cancer care together with chemotherapy, radiation therapy, and surgery. This introductory chapter provides a brief overview of the different types of cancer immunotherapies currently available, their mechanisms of action, and the benefits and potential side effects. Despite the success of these emerging therapies, resistance remains a genuine concern. Thus, mechanisms of resistance to immunotherapy are also briefly discussed. In addition, an overview of the various combination therapies such as chemotherapy, radiation therapy, and targeted therapy, that are currently used in combination with cancer immunotherapy, is presented. Finally, the chapter highlights how a "Team Medicine" approach could enable all eligible cancer patients to receive this promising treatment to treat their respective cancer types. More, detailed information regarding the different immunotherapies as well as their combinations when applicable in different cancers is discussed in the ensuing chapters dedicated to individual cancer type.

Immunotherapies continue to hold promise for the treatment of glioblastoma, a malignant central nervous system tumor. Thus far, success utilizing this approach has been limited. Negative trials with vaccines and immune checkpoint inhibitors have been unable to demonstrate improvement in survival, however, they have provided insights into hurdles which need to be overcome. Ongoing investigations into modulation of the highly suppressed tumor immune microenvironment, direct simulation of the immune system for proinflammatory effect, and the use of cellular therapies will help inform future therapeutic directions.

Head and neck cancer (HNC) is the seventh most common cancer worldwide, with incidence growing every year. While the standard regimen of surgery, chemotherapy, radiotherapy, targeted anti-EGFR therapy, and immune checkpoint inhibition are effective in a subset of patients, therapeutic resistance is a persistent challenge for managing this disease. The use of immunotherapeutic agents to treat HNC has risen over recent years, with advances in immune checkpoint inhibition, targeted therapy with bispecific antibodies, modified cytokine delivery, adoptive cell therapy, and virus-based therapeutics making their way into clinical trials for HNC. This chapter also discusses ongoing investigations into combinatorial strategies and biomarkers aimed at improving outcomes for patients with HNC.