Journal of cancer immunology最新文献

{"title":"Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma.","authors":"Aakash Patel, Daniel I Bisno, Hiren V Patel, Saum Ghodoussipour, Biren Saraiya, Tina Mayer, Eric A Singer","doi":"10.33696/cancerimmunol.3.047","DOIUrl":"10.33696/cancerimmunol.3.047","url":null,"abstract":"<p><p>Urothelial carcinoma is one of the most common cancers in the United States, yet outcomes are historically suboptimal. Since 2016, the approval of five programmed cell death 1 and programmed death-ligand 1 immune checkpoint inhibitors for locally advanced and metastatic urothelial carcinoma has led to improved oncologic outcomes for many patients in the second-line setting. Two checkpoint inhibitors, pembrolizumab and atezolizumab subsequently earned approval for first-fine therapy with restricted indications. More recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive high-risk non-muscle invasive bladder cancer, opening the door for other immune checkpoint inhibitors to be integrated into treatment in earlier disease stages. Recent bacillus Calmette-Guérin shortages have highlighted the need for alternative treatment options for patients with non-muscle invasive bladder cancer. Currently, there are no FDA-approved checkpoint inhibitors for non-metastatic muscle-invasive bladder cancer. Furthermore, many patients are ineligible for standard cisplatin-based chemotherapy regimens. Numerous ongoing clinical trials are employing immune checkpoint inhibitors for muscle-invasive bladder cancer patients in the neoadjuvant, adjuvant, perioperative, and bladder-sparing setting. Although up to 10% of urothelial carcinoma tumors arise in the upper urinary tract, few studies are designed for this population. We highlight the need for more trials designed for patients with upper tract disease. Overall, there are numerous clinical trials investigating the safety and efficacy of immune checkpoint inhibitors in all stages of disease as single-agents and combined with dual-immune checkpoint inhibition, chemotherapy, radiotherapy, and other pharmacologic agents. As the field continues to evolve rapidly, we aim to provide an overview of recent and ongoing immunotherapy clinical trials in urothelial carcinoma.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"3 2","pages":"115-136"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39185137","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":"Humanized Chimeric Antigen Receptor (CAR) T cells.","authors":"Pouya Safarzadeh Kozani,&nbsp;Pooria Safarzadeh Kozani,&nbsp;Roddy S O'Connor","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"3 4","pages":"183-187"},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39599054","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":"Hepatocellular Carcinoma: Animal Models Available to Characterize Tumor Immunology and Optimize Treatment Development","authors":"Gaël S. Roth, Z. Jílková, T. Decaens","doi":"10.33696/CANCERIMMUNOL.2.026","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.026","url":null,"abstract":"Hepatocellular carcinoma (HCC) is the second cause of cancer-related death worldwide with almost 1 million new cases per year. At the diagnosis, 70% of patients have only access to a palliative treatment [1,2] with few therapeutic options mostly represented by tyrosine kinase inhibitors such as sorafenib [3] and lenvatinib [4] in first line; regorafenib [5] and cabozantinib [6] in second line. HCC occurs on a cirrhotic liver in more than 90% of cases and liver is a singular organ from an immunological point of view. Cirrhosis modulates liver immune landscape through chronic alterations such as inflammation and fibrosis and these immune changes may induce aberrant immunotolerance through the activation of multiple pathways involving major immune functions such as antigen presentation or lymphocytes’ exhaustion. These modifications lead to failure to immunosurveillance systems and allow tumor initiation and progression [7]. For that reason, HCC seems to be a good candidate to immunostimulatory therapies aiming to restore anticancer immunity. These therapies are currently strongly studied in this pathology with the advent of monoclonal antibodies directed against immune checkpoints, especially against PD-1/PD-L1 pathway. Two new combination therapies particularly stand out: atezolizumab (anti-PD-L1) bevacizumab (anti-angiogenic) which is becoming the new standard in first line [8] and durvalumab (anti-PD-L1) tremelimumab (anti-CTLA4) [9]. Nonetheless, a large proportion of patients do not respond to these treatments and complex physiopathological mechanisms involved in HCC oncogenesis, as well as resistance pathways activated during these immunotherapies are still poorly understood.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43689761","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":"Immunotherapy in Pediatric Acute Lymphoblastic Leukemia","authors":"Julie M. Asare, C. Rabik, S. Cooper, P. Brown","doi":"10.33696/CANCERIMMUNOL.2.028","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.028","url":null,"abstract":"Approximately 85% of ALL cases are B-ALL [2]. Cure rates for B-ALL significantly rose over the past five decades from 10% to 90% [1-3] due to multi-agent chemotherapy regiments, CNS prophylaxis and better risk stratification [3]. Despite these successes, about 2% of patients are refractory to chemotherapy and another 10% to 15% of patients will relapse [4]. Treatment for these patients remains a therapeutic challenge. Event free survival for Abstract","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49268912","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":"Susceptibility of Malignant Brain Tumors to 5-aminolaevulinic Acid Mediated Photodynamic Therapy: Direct Phototoxicity and Immunological Effects","authors":"A. Datsi, R. Sorg","doi":"10.33696/CANCERIMMUNOL.2.033","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.033","url":null,"abstract":"Recently we published the article ‘Accumulation of protoporphyrin IX in medulloblastoma cell lines and sensitivity to subsequent photodynamic treatment’ [1]. In this commentary, we review protoporphyrin IX accumulation after application of 5-aminolaevulinic acid and the resulting sensitivity of medulloblastoma cells to photodynamic therapy. We compare the results to glioblastoma cells, including glioblastoma stem-like cells, and address the contribution of the transporter adenosine triphosphate binding cassette subfamily G member 2 (ABCG2) as well as the enzyme ferrochelatase to the process. We discuss possible strategies to improve efficiency of photodynamic therapy, particularly in the clinical setting and highlight the contribution of the antitumoral immune response to the efficacy of this novel treatment modality for brain tumors.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44804703","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":"Management of Appendiceal Neuroendocrine Tumors: Beyond Tumor Size","authors":"J. Landry, Y. B. Mattison, R. Ramirez, J. Boudreaux, E. Woltering, M. Maluccio, R. Thiagarajan","doi":"10.33696/CANCERIMMUNOL.2.030","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.030","url":null,"abstract":"Jace P. Landry1*, Yvette B. Mattison1,2,3, Robert A. Ramirez2,3, J. Philip Boudreaux1,2,3, Eugene A. Woltering1,2,3, Mary A. Maluccio1,2,3, Ramcharan Thiagarajan1,2,3 1Louisiana State University Health Sciences Center – Department of Surgery, New Orleans, LA, USA 2The New Orleans Louisiana Neuroendocrine Tumor Specialists, New Orleans, LA, USA 3Ochsner Medical Center, Neuroendocrine Tumor Clinic, Kenner, LA , USA *Correspondence should be addressed to Jace Philip Landry; jlan10@lsuhsc.edu","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43715609","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":"High Lymph Node Positive to Sampled Ratio as a Potential Indication for Postoperative Radiation Therapy in Patients with pN2 Non-small-cell Lung Cancer","authors":"N. Mankuzhy, M. Almahariq, C. Stevens, T. Quinn","doi":"10.33696/CANCERIMMUNOL.2.032","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.032","url":null,"abstract":"Despite advances in cancer treatment and screening, lung cancer remains the leading cause of cancer death in the United States [1]. The majority of cases are locally advanced non-small cell lung cancer (NSCLC), treatment of which usually includes a bior tri-modality therapy utilizing a combination of surgery, chemotherapy, and radiation therapy. For patients initially treated with surgery, use of postoperative radiation therapy (PORT) for completely resected NSCLC has remained controversial since the initial publication of the PORT meta-analysis in 1998 [2]. Stewart et al. reported an overall detriment of PORT on overall survival (OS), which was proposed to be linked to factors outside of inferior cancer control, such as adverse treatment effects. However, no clear impairment to OS existed in patients found to have mediastinal lymph node involvement (pN2), leading to multiple single-institution and database registry analyses investigating this question. These studies are limited by indication bias inherent to retrospective design, but provided justification of continued use of PORT in pN2 disease. Despite absence of high-level evidence, PORT has remained standard of care for this subset of NSCLC due to benefits in locoregional control and OS as indicated by American Society for Radiation Oncology (ASTRO) practice guidelines [3]. Abstract","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46749610","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":"SPANX Regulation of LAMIN A/C Network: Perspectives in Cancer and Laminopathies","authors":"I. Lazar, Bertrand Fabre","doi":"10.33696/CANCERIMMUNOL.2.034","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.034","url":null,"abstract":"216 Cancer/testis antigens (CTA) are tumor antigens whose expression is normally restricted to the testis. More than half of CTA genes are located on the X chromosome and form a branch called X-CTA [1]. Unlike the remaining CTA genes located throughout the genome, multigene X-CTA families are present as clusters on the X chromosome. Among them, the Sperm Protein Associated with the Nucleus on the X chromosome (SPANX) family is composed by five members [SPANX-A1, -A2 (-A1 and -A2 being two copies of the same gene), -B1, -C and -D]. As SPANX proteins are highly homologous and cannot be distinguished by antibody-based techniques, unless stated otherwise, hereafter we will use the term “SPANX” to refer to these five proteins. SPANX proteins are expressed post-meiosis in round and elongating spermatids [2], and their expression positively correlates with male fertility measured by pregnancy rate [3]. SPANX function in spermatids and spermatozoa is poorly characterized. However, cell fractionation analysis revealed that SPANX is abnormally distributed in samples with low spermatozoa motility [4] suggesting that SPANX is related to this process. Furthermore, identification of SPANX partners in spermatozoa has revealed proteins functioning in nuclear organization, mitochondrial metabolism and flagellar motility [5]. The discovery that SPANX genes are expressed in tumor cells was reported in a search for metastasis-specific genes in the melanoma line 1F6m, a metastatic variant of the parental 1F6 line [6]. Since then, SPANX gene expression has been observed in numerous malignancies, including breast cancer and hematological malignancies, as well as melanoma [6,7].","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43276312","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":"Ovarian Function Suppression Plus Aromatase Inhibitors or Tamoxifen in Premenopausal HR-positive Breast Cancer","authors":"Xueqin Xie, Yiqun Yao, Dianlong Zhang","doi":"10.33696/CANCERIMMUNOL.2.029","DOIUrl":"https://doi.org/10.33696/CANCERIMMUNOL.2.029","url":null,"abstract":"Breast cancer is the most common type of malignant tumor in women, accounting for 30% of women’s cancer, while the mortality rate ranks second among women’s cancer [1]. Twenty-five percent of all breast cancer patients are premenopausal patients, and 7% of patients are younger than 40 years old [2]. According to statistics analysis, nearly 60% of premenopausal breast cancer patients aging 15-39 years old are HR-positive [3]. Adjuvant endocrine therapy plays an increasingly important role in these patients due to its high efficiency and low toxicity. It is an important means to reduce the risk of recurrence of these patients. 5-10 years tamoxifen (TAM) treatment is the gold standard for adjuvant endocrine therapy in premenopausal hormone receptor (HR) positive breast cancer patients [4-9]. Since the discovery of aromatase inhibitors (AIs), various clinical studies [10-13] have proved that AIs are better than TAM for adjuvant treatment of early postmenopausal breast cancer, and AIs have become the first-line therapy for postmenopausal women with early breast cancer. Ovarian function suppression (OFS) has been used in the treatment of breast cancer for decades. Earlier studies have confirmed that OFS alone can reduce the risk of recurrence of premenopausal breast cancer patients and improved survival [14-15]. A multicenter retrospective cohort study of premenopausal women with stage I to III hormone receptor-positive breast cancer diagnosed from 2006 to 2015 showed in the real-world setting that after 2014, the number of people using OFS increased. 25% menopausal patients used OFS, of which more than 30% of patients used OFS plus an aromatase inhibitor (AI) [16]. OFS application adds benefits to TAM as a study demonstrated that when compared with using of TAM alone, the addition of OFS to TAM reduces the patient’s estradiol level, and at the same time significantly reduces the patient’s breast density and endometrial thickness [17]. The application of OFS also makes AIs applicable to premenopausal women. Generally speaking, AIs are not used in premenopausal patients, because ovarian function will increase the production of aromatase, causing AIs to lose efficacy. After using Als in postmenopausal patients, the estrogen concentration of the patients may not be detectable [18]. Premenopausal patients using exemestane in addition to Abstract","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48764675","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":"Mitochondria Autoimmunity and MNRR1 in Breast Carcinogenesis: A Review.","authors":"Félix Fernández Madrid, Lawrence I Grossman, Siddhesh Aras","doi":"10.33696/cancerimmunol.2.027","DOIUrl":"10.33696/cancerimmunol.2.027","url":null,"abstract":"<p><p>We review here the evidence for participation of mitochondrial autoimmunity in BC inception and progression and propose a new paradigm that may challenge the prevailing thinking in oncogenesis by suggesting that mitochondrial autoimmunity is a major contributor to breast carcinogenesis and probably to the inception and progression of other solid tumors. It has been shown that MNRR1 mediated mitochondrial-nuclear function promotes BC cell growth and migration and the development of metastasis and constitutes a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis. The resemblance of the autoantibody profile in BC detected by IFA with that in the rheumatic autoimmune diseases suggested that studies on the autoantibody response to tumor associated antigens and the characterization of the mtDNA- and nDNA-encoded antigens may provide functional data on breast carcinogenesis. We also review the studies supporting the view that a panel of autoreactive nDNA-encoded mitochondrial antigens in addition to MNRR1 may be involved in breast carcinogenesis. These include GAPDH, PKM2, GSTP1, SPATA5, MFF, ncRNA PINK1-AS/DDOST as probably contributing to BC progression and metastases and the evidence suggesting that DDX21 orchestrates a complex signaling network with participation of JUND and ATF3 driving chronic inflammation and breast tumorigenesis. We suggest that the widespread autoreactivity of mtDNA- and nDNA-encoded mitochondrial proteins found in BC sera may be the reflection of autoimmunity triggered by mitochondrial and non-mitochondrial tumor associated antigens involved in multiple tumorigenic pathways. Furthermore, we suggest that mitochondrial proteins may contribute to mitochondrial dysfunction in BC even if mitochondrial respiration is found to be within normal limits. However, although the studies show that mitochondrial autoimmunity is a major factor in breast cancer inception and progression, it is not the only factor since there is a multiplex autoantibody profile targeting centrosome and stem cell antigens as well as anti-idiotypic antibodies, revealing the complex signaling network involved in breast carcinogenesis. In summary, the studies reviewed here open new, unexpected therapeutic avenues for cancer prevention and treatment of patients with cancer derived from an entirely new perspective of breast carcinogenesis.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"2 4","pages":"138-158"},"PeriodicalIF":0.0,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25392324","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}