Journal of cancer immunology最新文献

{"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}

{"title":"Purinergic System and Cervical Cancer: Perspectives","authors":"Marta Schmidt Pfaffenzeller, Maria Luiza Mukai Franciosi, A. Wagner, A. Cardoso","doi":"10.33696/cancerimmunol.2.017","DOIUrl":"https://doi.org/10.33696/cancerimmunol.2.017","url":null,"abstract":"62 We have recently published an article entitled “Purinergic signaling and tumor microenvironment in cervical Cancer” [1]. In this paper, we reviewed the last studies about purinergic signaling and cervical cancer, highlighting the intrinsic factors related to the inflammatory process, such as extracellular nucleotides and adenosine components of the purinergic system. Our review focused on the role of the purinergic system in cervical cancer, especially regarding the interaction of extracellular nucleotides with their respective receptors expressed in the tumor microenvironment of cervical cancer and their role in the host immune response. Here we comment the main points of our work and suggest further basic and clinical investigations related to these key factors.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47815661","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":"Progress in Diagnosis and Treatment of Immune Checkpoint Inhibitor-Associated Cardiotoxicity","authors":"Feng Wang, S. Qin","doi":"10.33696/cancerimmunol.2.022","DOIUrl":"https://doi.org/10.33696/cancerimmunol.2.022","url":null,"abstract":"Immune checkpoint inhibitor (ICI)-associated cardiotoxicity is a rare immune-related adverse event with high mortality. In recent years, more and more reports were reported. It is urgent to improve understanding and management. Cardiac toxicity often occurs in the early stage after ICI treatment, and its clinical manifestations are diverse and nonspecific, and its pathogenesis is still unclear. Among them, the incidence of immune myocarditis is more than 1%, which can be manifested as fulminant, acute or chronic. Some asymptomatic patients may experience an incubation period to develop acute or fulminant myocarditis, and the mortality of myocarditis can be as high as 50%. Regular monitoring of cardiac biomarkers and ECG is helpful for early diagnosis. Myocardial and endocardial biopsy is the gold standard for diagnosis. Immune myocarditis is sensitive to glucocorticoid. The use of glucocorticoid should be early and sufficient. Asymptomatic myocarditis often has a good outcome if treated in time. The cardiologist’s assistance in diagnosis and treatment is helpful to improve the prognosis.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46397198","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":"Immunological Features with DNA Microsatellite Alterations in Patients with Colorectal Cancer.","authors":"Maide O Raeker,&nbsp;John M Carethers","doi":"10.33696/cancerimmunol.2.024","DOIUrl":"https://doi.org/10.33696/cancerimmunol.2.024","url":null,"abstract":"<p><p>Competent human DNA mismatch repair (MMR) corrects DNA polymerase mistakes made during cell replication to maintain complete DNA fidelity in daughter cells; faulty DNA MMR occurs in the setting of inflammation and neoplasia, creating base substitutions (e.g. point mutations) and frameshift mutations at DNA microsatellite sequences in progeny cells. Frameshift mutations at DNA microsatellite sequences are a detected biomarker termed microsatellite instability (MSI) for human disease, as this marker can prognosticate and determine therapeutic approaches for patients with cancer. There are two types of MSI: MSI-High (MSI-H), defined by frameshifts at mono- and di-nucleotide microsatellite sequences, and elevated microsatellite alterations at selected tetranucleotide repeats or EMAST, defined by frameshifts in di- and tetranucleotide microsatellite sequences but not mononucleotide sequences. Patients with colorectal cancers (CRCs) manifesting MSI-H demonstrate improved survival over patients without an MSI-H tumor, driven by the generation of immunogenic neoantigens caused by novel truncated proteins from genes whose sequences contain coding microsatellites; these patients' tumors contain hundreds of somatic mutations, and show responsiveness to treatment with immune checkpoint inhibitors. Patients with CRCs manifesting EMAST demonstrate poor survival over patients without an EMAST tumor, and may be driven by a more dominant defect in double strand break repair attributed to the MMR protein MSH3 over its frameshift correcting function; these patients' tumors often have a component of inflammation (and are also termed inflammation-associated microsatellite alterations) and show less somatic mutations and lack coding mononucleotide frameshift mutations that seem to generate the neoantigens seen in the majority of MSI-H tumors. Overall, both types of MSI are biomarkers that can prognosticate patients with CRC, can be tested for simultaneously in marker panels, and informs the approach to specific therapy including immunotherapy for their cancers.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"2 3","pages":"116-127"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523708/pdf/nihms-1631794.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38537039","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":"Autophagy: When to strike?","authors":"Shadi Zahedi,&nbsp;Jean M Mulcahy Levy","doi":"10.33696/cancerimmunol.2.008","DOIUrl":"https://doi.org/10.33696/cancerimmunol.2.008","url":null,"abstract":"In cancer, autophagy seems to have a dual role in tumor cell survival and death. During early stages of tumorigenesis, autophagy can limit tumor growth, however, in advanced cancers it may facilitate tumor progression as a protective mechanism against various stress conditions [1]. Given that tumors are frequently exposed to environmental stresses such as nutrient deprivation, low PH and hypoxic conditions, inhibiting autophagy appears to be a promising target for therapy. In fact, we and others have shown that targeting this pathway in combination with existing therapies can improve therapeutic outcome in some cancers [2–6].","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"2 1","pages":"13-16"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37979687","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":"The Role of ERO1α in Modulating Cancer Progression and Immune Escape.","authors":"Brennan D Johnson, Werner J Geldenhuys, Lori A Hazlehurst","doi":"10.33696/cancerimmunol.2.023","DOIUrl":"10.33696/cancerimmunol.2.023","url":null,"abstract":"<p><p>Endoplasmic reticulum oxidoreductin-1 alpha (ERO1α) was originally shown to be an endoplasmic reticulum (ER) resident protein undergoing oxidative cycles in concert with protein disulfide isomerase (PDI) to promote proper protein folding and to maintain homeostasis within the ER. ERO1α belongs to the flavoprotein family containing a flavin adenine dinucleotide utilized in transferring of electrons during oxidation-reduction cycles. This family is used to maintain redox potentials and protein homeostasis within the ER. ERO1α's location and function has since been shown to exist beyond the ER. Originally thought to exist solely in the ER, it has since been found to exist in the golgi apparatus, as well as in exosomes purified from patient samples. Besides aiding in protein folding of transmembrane and secretory proteins in conjunction with PDI, ERO1α is also known for formation of <i>de novo</i> disulfide bridges. Public databases, such as the Cancer Genome Atlas (TCGA) and The Protein Atlas, reveal ERO1α as a poor prognostic marker in multiple disease settings. Recent evidence indicates that ERO1α expression in tumor cells is a critical determinant of metastasis. However, the impact of increased ERO1α expression in tumor cells extends into the tumor microenvironment. Secretory proteins requiring ERO1α expression for proper folding have been implicated as being involved in immune escape through promotion of upregulation of programmed death ligand-1 (PD-L1) and stimulation of polymorphonuclear myeloid derived suppressor cells (PMN-MDSC's) via secretion of granulocytic colony stimulating factor (G-CSF). Hereby, ERO1α plays a pivotal role in cancer progression and potentially immune escape; making ERO1α an emerging attractive putative target for the treatment of cancer.</p>","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"2 3","pages":"103-115"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25392379","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":"pMB FLASH - Status and Perspectives of Combining Proton Minibeam with FLASH Radiotherapy","authors":"Judith Reindl and Stefanie Girst","doi":"10.33696/cancerimmunol.1.003","DOIUrl":"https://doi.org/10.33696/cancerimmunol.1.003","url":null,"abstract":"Proton minibeam radiotherapy (pMBRT) is an external beam radiotherapy method with reduced side effects by taking advantage of spatial fractionation in the normal tissue. Due to scattering, the delivered small beams widen in the tissue ensuring a homogeneous dose distribution in the tumor. In this review, the physical and biological principles regarding dose distribution and healing effects are explained. In the last decade, several preclinical studies have been conducted addressing normal tissue sparing and tumor control in-vitro and in-vivo, using human skin tissue and mouse or rat models. The major results acquired in these studies are summarized. A further newly emerging therapy method is FLASH radiotherapy, i.e. the treatment using ultra-high dose rates. The possibility of combining these methods in proton minibeam FLASH therapy (pMB FLASH) is worked out. Additionally, technical feasibility and limitations will be discussed by looking at simulations as well as preclinical studies and also pointing out new ways of delivering the desired tumor dose, such as interlacing. We will also highlight the opportunities that emerge regarding high dose radiation, hypofractionation and the combination with immunotherapy.","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44394762","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":"Chimeric Antigen Receptor CAR NK Cells Emerging Immunotherapy for the Treatment of Cancer","authors":"S. Deshmukh","doi":"10.33696/cancerimmunol.1.002","DOIUrl":"https://doi.org/10.33696/cancerimmunol.1.002","url":null,"abstract":"","PeriodicalId":73633,"journal":{"name":"Journal of cancer immunology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69669481","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}