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The Oncologist Jun 2023T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
T-cell receptor (TCR-T) therapies are based on the expression of an introduced TCR targeting a tumor associated antigen (TAA) which has been studied in several trials in cutaneous melanoma. We conducted a systematic review and meta-analysis aiming to assess the primary efficacy of TCR-based adoptive cell therapy in cutaneous melanoma.
METHODS
We searched through PubMed electronic database from its inception until May 21, 2022. Primary endpoints were pooled objective response rate (ORR) and disease control rate (DCR). We conducted logistic regression analyses to identify potential predictive factors for tumor response.
RESULTS
From 187 patients, 50 showed an objective response (pooled ORR 28%; 95% CI, 20%-37%) and a pooled DCR of 38% (95% CI, 27%-50%). Median PFS was 2, 9 months (95% CI, 1.4-3.1). A trend toward higher PFS was demonstrated for patients treated with cancer/testis antigens targeting TCR-T cells (HR 0.91 95% CI, 0.64-1.3, P = .61) among whom, patients treated with NYESO-1 targeting TCR-T showed a significantly higher PFS (HR 0.63 95% CI, 0.64-0.98, P = .03). In addition, the number of infused cells was associated with a significantly higher likelihood of tumor response (OR 6.61; 95% CI, 1.68-21.6; P = .007).
CONCLUSION
TCR-T therapy shows promising results in terms of antitumor activity and survival similar to those reported for TILs with a significantly higher benefit for cancer/testis antigens targeting cells. Since TCR-based therapy shows advantages of great potential over classic ACT strategies, further research in solid cancers is warranted (PROSPERO ID CRD42022328011).
Topics: Male; Humans; Melanoma; Skin Neoplasms; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell; Melanoma, Cutaneous Malignant
PubMed: 37036865
DOI: 10.1093/oncolo/oyad078 -
Phenomics (Cham, Switzerland) Apr 2022Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of... (Review)
Review
Increasing evidence has demonstrated that abnormal epigenetic modifications are strongly related to cancer initiation. Thus, sensitive and specific detection of epigenetic modifications could markedly improve biological investigations and cancer precision medicine. A rapid development of molecular imaging approaches for the diagnosis and prognosis of cancer has been observed during the past few years. Various biomarkers unique to epigenetic modifications and targeted imaging probes have been characterized and used to discriminate cancer from healthy tissues, as well as evaluate therapeutic responses. In this study, we summarize the latest studies associated with optical molecular imaging of epigenetic modification targets, such as those involving DNA methylation, histone modification, noncoding RNA regulation, and chromosome remodeling, and further review their clinical application on cancer diagnosis and treatment. Lastly, we further propose the future directions for precision imaging of epigenetic modification in cancer. Supported by promising clinical and preclinical studies associated with optical molecular imaging technology and epigenetic drugs, the central role of epigenetics in cancer should be increasingly recognized and accepted.
PubMed: 36939779
DOI: 10.1007/s43657-021-00041-y -
International Journal of Oral and... Jan 2021The purpose of this review was to integrate the clinical, radiological, microscopic, and molecular data of published cherubism cases, in addition to therapeutic...
The purpose of this review was to integrate the clinical, radiological, microscopic, and molecular data of published cherubism cases, in addition to therapeutic approaches, to provide more concise information about the disease. An electronic search was undertaken in September 2019. Eligibility criteria included publications having enough clinical, radiological, and histological information to confirm the diagnosis. A total of 260 publications reporting 513 cherubism cases were included. Familial history was observed in 310/458 cases (67.7%). SH3BP2 mutations were reported in 101/108 cases (93.5%) and mainly occurred at protein residues 415, 418, 419, and 420. Retrospective clinical grading was possible in 175 cases. Advanced clinical grading was associated with tooth agenesis, but not with other clinical, radiological, and genetic features. Specific amino acid substitutions of SH3BP2 mutations were not associated with the clinical grading of the disease. 'Wait and see' was the most common therapeutic approach. In a small number of cases, drugs were used in the treatment, with variable response. In conclusion, there is no clear correlation between the genotype and the phenotype of the disease, but additional genomic and gene expression regulation information is necessary for a better understanding of cherubism.
Topics: Adaptor Proteins, Signal Transducing; Cherubism; Humans; Mutation; Phenotype; Retrospective Studies
PubMed: 32620450
DOI: 10.1016/j.ijom.2020.05.021 -
Cancer Medicine Sep 2023The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The main therapy for rectal cancer patients is neoadjuvant therapy (NT) followed by surgery. Immune biomarkers are emerging as potential predictors of the response to NT. We performed a meta-analysis to estimate their predictive significance.
METHODS
A systematic literature search of PubMed, Ovid MEDLINE and EMBASE databases was performed to identify eligible studies. Studies on patients with rectal cancer undergoing NT in which the predictive significance of at least one of the immunological markers of interest was assessed by immunohistochemistry (IHC) in pretreatment biopsies were included.
RESULTS
Seventeen studies reporting sufficient data met the inclusion criteria for meta-analysis. High levels of total CD3+, CD4+ and CD8+ tumor infiltrating lymphocytes (TILs), as well as stromal and intraepithelial CD8+ compartments, significantly predicted good pathological response to NT. Moreover, high levels of total (tumoral and immune cell expression) PD-L1 resulted associated to a good pathological response. On the contrary, high levels of intraepithelial CD4+ TILs were correlated with poor pathological response. FoxP3+ TILs, tumoral PD-L1 and CTLA-4 were not correlated to the treatment response.
CONCLUSION
This meta-analysis indicated that high-density TILs might be predictive biomarkers of pathological response in patients that underwent NT for rectal cancer.
Topics: Humans; B7-H1 Antigen; Neoadjuvant Therapy; CD8-Positive T-Lymphocytes; Biomarkers; Rectal Neoplasms; Biopsy; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 37537787
DOI: 10.1002/cam4.6423 -
Journal of Cachexia, Sarcopenia and... Oct 2022One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular... (Meta-Analysis)
Meta-Analysis Review
One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular basis of muscle memory remains to be fully elucidated, one potential mechanism thought to mediate muscle memory is the permanent retention of myonuclei acquired during the initial phase of hypertrophic growth. However, myonuclear permanence is debated and would benefit from a meta-analysis to clarify the current state of the field for this important aspect of skeletal muscle plasticity. The objective of this study was to perform a meta-analysis to assess the permanence of myonuclei associated with changes in physical activity and ageing. When available, the abundance of satellite cells (SCs) was also considered given their potential influence on changes in myonuclear abundance. One hundred forty-seven peer-reviewed articles were identified for inclusion across five separate meta-analyses; (1-2) human and rodent studies assessed muscle response to hypertrophy; (3-4) human and rodent studies assessed muscle response to atrophy; and (5) human studies assessed muscle response with ageing. Skeletal muscle hypertrophy was associated with higher myonuclear content that was retained in rodents, but not humans, with atrophy (SMD = -0.60, 95% CI -1.71 to 0.51, P = 0.29, and MD = 83.46, 95% CI -649.41 to 816.32, P = 0.82; respectively). Myonuclear and SC content were both lower following atrophy in humans (MD = -11, 95% CI -0.19 to -0.03, P = 0.005, and SMD = -0.49, 95% CI -0.77 to -0.22, P = 0.0005; respectively), although the response in rodents was affected by the type of muscle under consideration and the mode of atrophy. Whereas rodent myonuclei were found to be more permanent regardless of the mode of atrophy, atrophy of ≥30% was associated with a reduction in myonuclear content (SMD = -1.02, 95% CI -1.53 to -0.51, P = 0.0001). In humans, sarcopenia was accompanied by a lower myonuclear and SC content (MD = 0.47, 95% CI 0.09 to 0.85, P = 0.02, and SMD = 0.78, 95% CI 0.37-1.19, P = 0.0002; respectively). The major finding from the present meta-analysis is that myonuclei are not permanent but are lost during periods of atrophy and with ageing. These findings do not support the concept of skeletal muscle memory based on the permanence of myonuclei and suggest other mechanisms, such as epigenetics, may have a more important role in mediating this aspect of skeletal muscle plasticity.
Topics: Animals; Atrophy; Humans; Hypertrophy; Muscle Fibers, Skeletal; Muscle, Skeletal; Sarcopenia
PubMed: 35961635
DOI: 10.1002/jcsm.13043 -
Neurology. Clinical Practice Aug 2021There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose... (Review)
Review
BACKGROUND
There is an unmet need for reliable biomarkers to predict disease severity, prognosis, and treatment effect in patients with spinal muscular atrophy (SMA). The purpose of this review is to evaluate the clinical utility of blood-based biomarkers in patients with SMA.
METHODS
A systematic review of MEDLINE, DARE, PEDro, PsycINFO, Cochrane Database, LILACS, OTSeeker, SpeechBITE, CINAHL, Scopus, Science Direct, clinicaltrial.gov, OpenGrey, and Google Scholar was performed with the last search data of June 30, 2019.
RESULTS
Survival motor neuron (SMN)-related biomarkers showed an important interpatient and cell variability with a wide overlap between SMA phenotypes and healthy controls. Several plasma protein analytes correlated with motor scores; however, validation studies are needed to rule out false positives. DNA methylation analysis distinguished between patients with mild/moderate SMA and healthy controls. Plasma phosphorylated neurofilament heavy chain (pNF-H) levels increased with disease severity and declined considerably after nusinersen treatment.
CONCLUSION
There is no sufficient evidence to support the clinical utility of SMN-related biomarkers to predict disease severity in SMA. pNF-H appears to be a promising biomarker of disease activity and treatment effect in SMA. Further studies should include longitudinal assessments of patients with SMA across functional groups and comparisons with age-matched healthy controls to evaluate the stability of putative biomarkers over time and in response to SMA therapeutics. PROSPERO registration: CRD42019139050.
PubMed: 34484951
DOI: 10.1212/CPJ.0000000000000872 -
Skin Research and Technology : Official... Jun 2023The incidence of alopecia areata (AA) has increased over the last few decades. Trichoscopy is a noninvasive procedure performed in dermatology clinics and is a helpful... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The incidence of alopecia areata (AA) has increased over the last few decades. Trichoscopy is a noninvasive procedure performed in dermatology clinics and is a helpful tool in determining the correct diagnosis of hair loss presentations.
OBJECTIVE
Through mapping the researches that have been done to represent the spectrum of trichoscopic findings in AA and to identify the most characteristic patterns.
METHODS
Thirty-nine studies were eligible for the quantitative analysis. Meta-analysis and subgroup analysis were performed.
RESULTS
Thirty-nine studies (29 cross-sectional, five retrospective, two descriptive, one case series, one observational, and one cohort) with a total of 3204 patients were included. About 66.7% of the studies were from Asia, 25.6% from Europe, and 7.7% from Africa. The most characteristic trichoscopic findings of AA were as follows; yellow dots, black dots, broken hairs, short vellus hairs, and tapering hairs.
CONCLUSION
There is no single pathognomonic diagnostic trichoscopic finding in AA rather than a constellation of characteristic findings. The five most characteristic trichoscopic findings in AA are: yellow dots, black dots, broken hairs, short vellus hairs, and tapering hairs. Yellow dots and short vellus hairs considered the most sensitive clues for AA, while black dots and tapering hairs are the most specific ones. Furthermore, trichoscopy is a useful tool that allows monitoring of response during the treatment of AA. Treatment responded cases will show an increase in short vellus hairs, but loss of tapering hairs, broken hairs, and black dots, while yellow dots are the least responsive to the treatment.
Topics: Alopecia Areata; Dermoscopy; Vitamin D Deficiency; Humans
PubMed: 37357664
DOI: 10.1111/srt.13378 -
Frontiers in Immunology 2023Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy... (Review)
Review
Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.
Topics: Humans; Immunotherapy; Bacteria; Neoplasms; Antigens, Bacterial; Bacterial Vaccines; Tumor Microenvironment
PubMed: 37600773
DOI: 10.3389/fimmu.2023.1140463 -
Pharmacology & Therapeutics Apr 2024Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of... (Review)
Review
Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies, including immunotherapy. Immune checkpoint inhibitors (ICIs) are currently used in the treatment of metastatic melanoma (MM) and despite being linked to an increase in patient survival, a high percentage of them still do not benefit from it. Accordingly, the number of therapeutic regimens for MM patients using ICIs either alone or in combination with other therapies has increased, together with the need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to reflect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review aims to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role in personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures.
Topics: Humans; Melanoma; Skin Neoplasms; Immunotherapy; Biomarkers
PubMed: 38367867
DOI: 10.1016/j.pharmthera.2024.108613 -
Cancer Treatment Reviews Mar 2017It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It is assumed that DNA methylation plays a key role in both tumour development and therapy resistance. Demethylating agents have been shown to be effective in the treatment of haematological malignancies. Based on encouraging preclinical results, demethylating agents may also be effective in solid tumours. This systematic review summarizes the evidence of the effect of demethylating agents on clinical response, methylation and the immune system in solid tumours.
METHODS
We conducted a systematic literature search from 1949 to December 2016, according to the PRISMA guidelines. Studies which evaluated treatment with azacitidine, decitabine, guadecitabine, hydralazine, procaine, MG98 and/or zebularine in patients with solid tumours were included. Data on clinical response, effects on methylation and immune response were extracted.
RESULTS
Fifty-eight studies were included: in 13 studies complete responses (CR) were observed, 35 studies showed partial responses (PR), 47 studies stable disease (SD) and all studies except two showed progressive disease (PD). Effects on global methylation were observed in 11/15 studies and demethylation/re-expression of tumour specific genes was seen in 15/17 studies. No clear correlation between (de)methylation and clinical response was observed. In 14 studies immune-related responses were reported, such as re-expression of cancer-testis antigens and upregulation of interferon genes.
CONCLUSION
Demethylating agents are able to improve clinical outcome and alter methylation status in patients with solid tumours. Although beneficial effect has been shown in individual patients, overall response is limited. Further research on biomarker predicting therapy efficacy is indicated, particularly in earlier stage and highly methylated tumours.
Topics: Antimetabolites, Antineoplastic; Azacitidine; Cytidine; DNA Methylation; Decitabine; Humans; Hydralazine; Immune System; Methylation; Neoplasms; Procaine; Treatment Outcome
PubMed: 28189913
DOI: 10.1016/j.ctrv.2017.01.004