Although high-risk human papillomaviruses (HPVs) are an important risk factor in the etiopathogenesis of cervical cancer, increasing evidence suggests that the ability to avoid immune surveillance seems to be linked to the transforming potential of HPV and a rapid progression to cancer. In other cancer models, IL-10 contributes to impair anti-tumor immune response either by downregulating human leukocyte antigen Class I (HLA-I) expression or by increasing HLA-G expression. To comprehend how these alterations could contribute to evasion of immune surveillance in cervical cancer, we analyzed HLA-I, HLA-G and IL-10 expressions by immunohistochemistry in 63 biopsies from patients with cervical intraepithelial neoplasia III (CIN-III) and cervical cancer. Immunohistochemistry showed absent or weak HLA-I expression in 50/59 cases. In these cases, a high percentage had loss of heterozygosis. IL-10 and HLA-G expression were observed in 46.6 and 27.6% of cases, respectively. Concurrent upregulation of IL-10 was found in 87.5% of HLA-G positive cases (p = 0.000). Similarly, a significant association between IL-10 expression and HLA-I downregulation was found (p = 0.028). Finally, we observed higher HLA-G expression in patients with HLA-I downregulation than in those with normal HLA-I expression (p = 0.004). Our results suggest that, in cervical cancer, the IL-10 expression may induce an immunosuppressive environment by upregulating HLA-G expression and downregulating HLA class I expression.
5 April 2016 in Journal of Experimental & Clinical Cancer Research
B-Acute lymphoblastic leukemia (B-ALL) represents a hematologic malignancy with poor clinical outcome and low survival rates in adult patients. Remission rates in Hispanic population are almost 30 % lower and Overall Survival (OS) nearly two years inferior than those reported in other ethnic groups. Only 61 % of Colombian adult patients with ALL achieve complete remission (CR), median overall survival is 11.3 months and event-free survival (EFS) is 7.34 months. Identification of prognostic factors is crucial for the application of proper treatment strategies and subsequently for successful outcome. Our goal was to identify a gene expression signature that might correlate with response to therapy and evaluate the utility of these as prognostic tool in hispanic patients. We included 43 adult patients newly diagnosed with B-ALL. We used microarray analysis in order to identify genes that distinguish poor from good response to treatment using differential gene expression analysis. The expression profile was validated by real-time PCR (RT-PCT). We identified 442 differentially expressed genes between responders and non-responders to induction treatment. Hierarchical analysis according to the expression of a 7-gene signature revealed 2 subsets of patients that differed in their clinical characteristics and outcome. Our study suggests that response to induction treatment and clinical outcome of Hispanic patients can be predicted from the onset of the disease and that gene expression profiles can be used to stratify patient risk adequately and accurately. The present study represents the first that shows the gene expression profiling of B-ALL Colombian adults and its relevance for stratification in the early course of disease.
Background and Objective: The discovery of novel molecular biomarkers via next-generation sequencing technologies has revolutionized how glioblastomas (GBMs) are classified nowadays. This has resulted in more precise diagnostic, prognostic, and therapeutic approaches to address this malignancy. The present work examines the applications of single-cell RNA sequencing (scRNA-seq) in GBM, focusing on its potential to address tumor complexity and therapeutic resistance and improve patient outcomes. Methods: A scoping review of original studies published between 2009 and 2024 was conducted using the PUBMED and EMBASE databases. Studies in English or Spanish related to single-cell analysis and GBM were included. Key Findings: The database search yielded 453 publications. Themes related to scRNA-seq applied for the diagnosis, prognosis, treatment, and understanding of the cancer biology of GBM were used as criteria for article selection. Of the 24 studies that were included in the review, 11 focused on the tumor microenvironment and cell subpopulations in GBM samples, 5 investigated the use of sequencing to elucidate the GBM cancer biology, 3 examined disease prognosis using sequencing models, 3 applied translational research through scRNA-seq, and 2 addressed treatment-related problems in GBM elucidated by scRNA-seq. Conclusions: This scoping review explored the various clinical applications of scRNA-seq technologies in approaching GBM. The findings highlight the utility of this technology in unraveling the complex cellular and immune landscapes of GBM, paving the way for improved diagnosis and personalized treatments. This cutting-edge approach might strengthen treatment strategies against tumor progression and recurrence, setting the stage for multi-targeted interventions that could significantly improve outcomes for patients with aggressive, treatment-resistant GBMs.
Summary: It has been suggested that tumour cell lysis by gamma‐radiation induces a tumoral antigen release eliciting an immune response. It is not clear how a specific immune response in cervical cancer patients is developed after radiotherapy. This study is an attempt to investigate the role of the human papillomavirus type 16 (HPV‐16) E7‐specific T helper response before and after radiotherapy. Lymphocytes were isolated from 32 cervical cancer patients before and after radiotherapy and from 16 healthy women. They were stimulated for 12 hr with autologous HPV‐16 E7‐pulsed monocyte‐derived dendritic cells or directly with HPV‐16 E7 synthetic peptides: E751–70, E765–84 and E779–98. The cells were stained for CD4, CD69, intracellular interferon‐γ (IFN‐γ) and interleukin‐4 (IL‐4) cytokines and analysed by flow cytometry. A specific CD4+ CD69+ IFN‐γ+ immune response against HPV‐16 E779–98 peptide was observed in 10 of 14 patients (71·4%) after treatment, compared with 4 of 14 (28·5%) before radiotherapy (P = 0·039); however, this response was not associated with a successful clinical response. Before treatment, 5 of 31 patients showed a HPV‐16 E779–98‐specific T helper type 2 (Th2) response. Interestingly, this response was significantly associated with a decrease in disease‐free survival (P = 0·027). These results suggest that a Th2‐type cellular response could be useful as a predictor of recurrence and poor prognosis. An increase of the HPV‐specific immune response was observed after radiotherapy; however, it is not enough to control completely the disease after treatment. Our results support that the E7‐specific T‐cell IFN‐γ response in cervical cancer patients, rather than reflecting the host’s capability of controlling tumour growth, might be an indicator for disease severity.
28 February 2017 in Journal of Experimental & Clinical Cancer Research
Survival of adults with B-Acute Lymphoblastic Leukemia requires accurate risk stratification of patients in order to provide the appropriate therapy. Contemporary techniques, using clinical and cytogenetic variables are incomplete for prognosis prediction. To improve the classification of adult patients diagnosed with B-ALL into prognosis groups, two strategies were examined and combined: the expression of the ID1/ID3/IGJ gene signature by RT-PCR and the immunophenotypic profile of 19 markers proposed in the EuroFlow protocol by Flow Cytometry in bone marrow samples. Both techniques were correlated to stratify patients into prognostic groups. An inverse relationship between survival and expression of the three-genes signature was observed and an immunophenotypic profile associated with clinical outcome was identified. Markers CD10 and CD20 were correlated with simultaneous overexpression of ID1, ID3 and IGJ. Patients with simultaneous expression of the poor prognosis gene signature and overexpression of CD10 or CD20, had worse Event Free Survival and Overall Survival than patients who had either the poor prognosis gene expression signature or only CD20 or CD10 overexpressed. By utilizing the combined evaluation of these two immunophenotypic markers along with the poor prognosis gene expression signature, the risk stratification can be significantly strengthened. Further studies including a large number of patients are needed to confirm these findings.