Journal of cancer immunology最新文献

{"title":"Combining EGFR and KRAS G12C Inhibitors for KRAS G12C Mutated Advanced Colorectal Cancer.","authors":"Hirotaka Miyashita, David S Hong","doi":"10.33696/cancerimmunol.6.086","DOIUrl":"10.33696/cancerimmunol.6.086","url":null,"abstract":"<p><p>KRAS is a commonly mutated gene in advanced colorectal cancer (CRC). Recently, inhibitors of KRAS G12C were developed and have shown promising efficacy for KRAS G12C mutated non-small cell lung cancer. However, KRAS G12C inhibitor monotherapy has not demonstrated excellent efficacy for KRAS G12C mutated advanced CRC due to multiple resistance mechanisms, especially receptor tyrosine kinase (RTK) signaling activation. To overcome this resistance mechanism, various combinations of epithelial growth factor receptor (EGFR) and KRAS G12C inhibitors, including panitumumab plus sotorasib, have been investigated in clinical trials. The combination of EGFR and KRAS G12C inhibitors for KRAS G12C mutated CRC demonstrated overall response rates ranging from 26% to 62.5% in seven clinical trials of phase I to III, whose data are available so far. The median progression-free survival in these trials ranged from 3.9 to 8.1 months. These efficacy data suggest that KRAS G12C inhibitor combination with EGFR inhibitors is more effective for KRAS G12C mutated advanced CRC than KRAS G12C inhibitor monotherapy. They also showed reasonable safety of the combination regimen. Based on these results, phase III clinical trials are being conducted to investigate EGFR and KRAS G12C inhibitor combinations as a first or second-line treatment for KRAS G12C mutated advanced CRC. Furthermore, other KRAS G12C inhibitors, KRAS G12D inhibitors, and pan-RAS inhibitors are being developed, which could make more patients with advanced CRC eligible for KRAS inhibition.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 2","pages":"62-69"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer.","authors":"Chethan Ramamurthy, Karen M Wheeler, Shaun Trecarten, Zaineb Hassouneh, Niannian Ji, Yifen Lee, Robert S Svatek, Neelam Mukherjee","doi":"10.33696/cancerimmunol.6.081","DOIUrl":"10.33696/cancerimmunol.6.081","url":null,"abstract":"<p><p>Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or adjuvant-remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment. The clinical trial was closed prematurely due to the industry's withdrawal of drug provision. Adverse events were observed in all patients; however, serious adverse events were not observed in any patient. A complete pathologic response was observed in 50% of the 4 patients enrolled. Response to treatment was significantly associated with elevated urinary T cells including CD8⁺ and IFNγ⁺ CD4⁺ T cells, suggesting potential reinforcement of immune responses by neoadjuvant αPD-1 and αCTLA-4 against bladder tumor cells. These findings suggest that combining chemotherapy and immunotherapy in the neoadjuvant setting could be safe. However, the complete response rate of this four-drug regimen was modest and emphasizes the need for randomized controlled trials to properly assess immunotherapy efficacy in the neoadjuvant setting. In corresponding murine studies, the MB49-met model consistently displayed widespread metastasis, including tumor growth in the lungs, liver, and bowel mesentery, within 20 days of subcutaneous transplantation. Mice receiving surgery plus neoadjuvant αPD-L1 or adjuvant αPD-L1 exhibited improved survival compared to those receiving only αPD-L1. However, no significant difference in survival was observed between the neoadjuvant and adjuvant αPD-L1 cohorts. Furthermore, the timing of neoadjuvant therapy administration (early vs. late) did not significantly impact survival. This study highlights the potential of perioperative immunotherapy in the treatment of locally advanced and metastatic bladder cancer.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 1","pages":"29-39"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11113005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphopeptide Neoantigens as Emerging Targets in Cancer Immunotherapy.","authors":"Tyagi Apoorvi, Patskovsky Yury, Voloshyna Iryna, Krogsgaard Michelle","doi":"10.33696/cancerimmunol.6.094","DOIUrl":"10.33696/cancerimmunol.6.094","url":null,"abstract":"<p><p>Protein post-translational modifications play a vital role in various cellular events essential for maintaining cellular physiology and homeostasis. In cancer cells, aberrant post-translational modifications such as glycosylation, acetylation, and phosphorylation on proteins can result in the generation of antigenic peptide variants presented in complex with MHC molecules. These modified peptides add to the class of tumorspecific antigens and offer promising avenues for targeted anti- cancer therapies. In this review, we focus on the role of phosphorylated peptides (p-peptides) in cancer immunity. We discuss the mechanisms by which the phosphorylated moiety modifies the structural features and binding properties of p-peptides with MHC, compared to their non-phosphorylated counterparts. Additionally, we review recent work on how the HLA-B*07-specific p-peptide, pMLL_747-755, interacts with its cognate TCR. Altogether, p-peptides are emerging as a novel class of tumor-specific antigens, expanding the range of targets in cancer immunotherapy.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 4","pages":"135-147"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Blood-based Metabolite Signature for Personalized Risk Assessment of Pancreatic Cancer.","authors":"Ricardo A León-Letelier, Yihui Chen, Riccardo Ballaro, Ehsan Irajizad, Kim-An Do, Anirban Maitra, Jianjun Zhang, C Max Schmidt, Johannes F Fahrmann","doi":"10.33696/cancerimmunol.6.095","DOIUrl":"10.33696/cancerimmunol.6.095","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 4","pages":"148-153"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Paradoxical AKT: Exploring the Promise and Challenges of PI3K/AKT/mTOR Targeted Therapies.","authors":"Gennie L Parkman, Sheri L Holmen","doi":"10.33696/cancerimmunol.6.089","DOIUrl":"10.33696/cancerimmunol.6.089","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 3","pages":"92-99"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Efficacy of CAR-T Cell Therapy: A Comprehensive Exploration of Cellular Strategies and Molecular Dynamics.","authors":"Mehmet A Baysal, Abhijit Chakraborty, Apostolia M Tsimberidou","doi":"10.33696/cancerimmunol.6.080","DOIUrl":"10.33696/cancerimmunol.6.080","url":null,"abstract":"<p><p>The emergence of chimeric antigen receptor T cell (CAR-T cell) therapy has revolutionized cancer treatment, particularly for hematologic malignancies. This commentary discusses developments in CAR-T cell therapy, focusing on the molecular mechanisms governing T cell fate and differentiation. Transcriptional and epigenetic factors play a pivotal role in determining the specificity, effectiveness, and durability of CAR-T cell therapy. Understanding these mechanisms is crucial to improve the efficacy and decrease the adverse events associated with CAR-T cell therapies, unlocking the full potential of these approaches. T cell differentiation in CAR-T cell product manufacturing plays an important role in clinical outcomes. A positive correlation exists between the clinical efficacy of CAR-T cell therapy and signatures of memory, whereas a negative correlation has been observed with signatures of effector function or exhaustion. The effectiveness of CAR-T cell products is likely influenced by T-cell frequency and by their ability to proliferate, which is closely linked to early T cell differentiation. The differentiation process involving distinct T memory cell subsets is initiated upon antigen elimination, indicating infection resolution. In chronic infections or cancer, T cells may undergo exhaustion, marked by continuous inhibitory receptor expression, decreased cytokine production, and diminished proliferative capacity. Other cell subsets, such as CD4⁺ T cells, innate-like T lymphocytes, NKT cells, and cord blood-derived hematopoietic stem cells, offer unique advantages in developing the next-generation CAR-T cell-based therapies. Future research should focus on optimizing T-cell-enhancing approaches and developing strategies to potentially cure patients with hematological diseases and solid tumors.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 1","pages":"20-28"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary: On the Emerging Role of Innate Lymphoid Cells in Bladder Cancer.","authors":"Zaineb Hassouneh, Gang Huang, Nu Zhang, Manjeet Rao, Neelam Mukherjee","doi":"10.33696/cancerimmunol.6.093","DOIUrl":"10.33696/cancerimmunol.6.093","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"6 3","pages":"125-134"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emulating the Role of Neutrophils in Head and Neck Cancer Microenvironment: Prognostic Role and Therapeutic Strategies","authors":"Khushwant Singh, P. K. Gautam","doi":"10.33696/cancerimmunol.5.076","DOIUrl":"https://doi.org/10.33696/cancerimmunol.5.076","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) are a group of cancers that affect various parts of the head and neck, such as the lip, oral cavity, oropharynx, hypopharynx, and nasopharynx. In India, it accounts for approximately 30–40% of all cancers, while in the United States, it represents around 4% of all cancer cases. HNSCC is a significant contributor to cancer-related deaths globally. While smoking is linked to HNSCC, recent research has confirmed the importance of the human papillomavirus (HPV) in its development. Additionally, HNSCC is characterized by immune deficiencies, where the tumor microenvironment alters immune cell activity to facilitate carcinogenesis. However, researchers have identified novel immunotherapeutic targets for HNSCC, mainly by studying the involvement of inflammatory cells such as neutrophils, eosinophils, and macrophages. Unfortunately, patients with recurring malignancy and distant metastases have limited treatment options, with a prognosis of less than one year. Platinum-based chemotherapy, cetuximab, and other conventional therapies are used to treat recurrent and metastatic HNSCC. The pro and anti-tumor roles of neutrophils in cancer and immunotherapy are explored in this study, with a focus on HNSCC. The primary objective is to increase our understanding of HNSCC biology and immunobiology to uncover viable therapeutic options that are both valid and less cytotoxic.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41455223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Factors of Nintedanib-docetaxel in Patients with Previously Treated Non-small-cell Lung Cancer","authors":"L. Cabezón-Gutiérrez, S. Custodio-Cabello, V. Pacheco-Barcia, Magda Palka-Kotlowska, Catalina Saez-Bertrand, Marta Blasco-Guerrero","doi":"10.33696/cancerimmunol.5.077","DOIUrl":"https://doi.org/10.33696/cancerimmunol.5.077","url":null,"abstract":"Background: In advanced non-small-cell lung cancer (NSCLC), second-line treatment with nintedanib plus docetaxel improves survival compared with docetaxel, especially in patients with adenocarcinoma histology who progressed within 9 months after the start of firstline treatment. It is therefore necessary to identify new biomarkers/prognostic factors that select the patients who benefit from this type of treatment.\u0000\u0000Patients and Methods: In this single-center retrospective study, we included patients treated NSCLC with nintedanib plus docetaxel in the second/third line and analyzed potential prognostic factors, many of them related to the inflammatory environment; PD-L1 expression levels, Lung Immune Prognostic Index (LIPI), derived neutrophil/lymphocytes ratio (dNLR), etc.\u0000\u0000Results: Among 16 patients included in this analysis, the overall response rate was 12.5%, median progression-free survival was 2 months (95% CI, 1.22-2.78) and median overall survival was 6 months (95% CI, 2.11-9.89). LDH level is the only variable related to the disease control rate (70% in normal versus 0% in elevated LDH). The variables analyzed with prognostic significance were; no brain metastases (HR 0.33, 95% CI 0.14-0.78; p=0.011), less than 3 metastatic sites (HR 0.33, 95% CI 0.14-0.78; p=0.011), the non-use of antiangiogenic drugs in the first line (HR 0.53, 95% CI: 0.29-0.98; p=0.043), the absence of elevated LDH at the start of treatment (HR 0.55, 95% CI: 0.3-1; p=0.051) and the absence of liver metastases (HR 0.55, 95% CI: 0.29-1; p=0.05).\u0000\u0000Conclusions: In NSCLC patients with less than three metastatic sites, no brain or liver metastases, normal LDH values and not previously treated with antiangiogenic drugs in the first line showed a better prognosis when treated with second/third line with nintedanib plus docetaxel.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48719982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial Mesenchymal Transition: The Ultimate Driver of Cancer on Difficult Paths","authors":"Devavrat Tripathi, P. Gupta, S. Kulkarni","doi":"10.33696/cancerimmunol.5.075","DOIUrl":"https://doi.org/10.33696/cancerimmunol.5.075","url":null,"abstract":"Metastasis is the perilous aspect of cancer and is responsible for 90% of deaths due to cancer. It represents an enigmatic and complex biological cascade that is poorly understood. The constant development in cancer research and the advent of new principles in metastasis have discovered some of the molecular keystones like epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) of this cascade. Acknowledgment of the communications between cancer cells and their micro-environment enlightens the biology of metastasis and allows us to understand the mechanism of EMT induction and its role in governing invasion, migration, plasticity, colonization, and therapeutic resistance. EMT is the principal reason behind the cancer cells’ complex behavior, tremendous plasticity, survival, and adoption in a constantly changing environment. Thus, EMT is a perfect driver mechanism to execute metastasis and develop resistance against conventional and targeted therapies. Studies have also discovered the role of EMT in CSCs generation and offered us prospects for evolving more effective treatments to target metastasis and improved patient prognosis.\u0000\u0000Our primary aim in the present review is to summarize the induction and role of EMT in cancer. This review not only discusses the role of EMT in metastasis but also uncovers the role of EMT in survival, metabolism, and CSCs generation. Further, in this review, we also discuss the strategy to target the EMT for the development of new and effective therapeutics for cancer management.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42190982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}