| 1. |
- Lauss, Martin, et al.
(författare)
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B Cells and Tertiary Lymphoid Structures : Friends or Foes in Cancer Immunotherapy?
- 2022
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 28:9, s. 1751-1758
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Forskningsöversikt (refereegranskat)abstract
- Tumor cells pose a challenge to the adaptive immune system, and its key cell types, T and B cells, have frequently been associated with an improved prognosis. The success of immune checkpoint blockade has confirmed the relevance of T cells. However, the role of B cells is increasingly recognized, and highlighted in this review. Recent data suggest that tumors contain a diverse set of B cells reflecting different developmental states and exerting functions such as antigen presentation, antibody production, and regulatory effects. Further, B cells are frequently located in tertiary lymphoid structures (TLS), which are immune cell niches that sustain an immune response at sites of chronic inflammation. TLSs in tumors display substantial heterogeneity, ranging from cell aggregates to mature structures with an active germinal center. Recent studies have provided insights into initiation, cellular and spatial composition, and function of TLS in a variety of cancer types; however, several critical issues still need to be resolved. Currently, initial reports are discerning the role of TLSs in immunotherapy, with the majority of studies observing TLSs to confer favorable patient outcome. Finally, TLS induction in tumors is evaluated, with the therapeutic aim to reactivate the host immune response.
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| 2. |
- Matikas, Alexios, et al.
(författare)
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Prognostic implications of PD-L1 expression in breast cancer : systematic review and meta-analysis of immunohistochemistry and pooled analysis of transcriptomic data
- 2019
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 25:18, s. 5717-5726
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: Conflicting data have been reported on the prognostic value of PD-L1 protein and gene expression in breast cancer.EXPERIMENTAL DESIGN: Medline, Embase, Cochrane Library and Web of Science Core Collection were searched and data were extracted independently by two researchers. Outcomes included pooled PD-L1 protein positivity in tumor cells, immune cells or both, per subtype and per antibody used; and its prognostic value for disease-free and overall survival. A pooled gene expression analysis of 39 publicly available transcriptomic datasets was also performed.RESULTS: Of the initial 4184 entries, 38 retrospective studies fulfilled the predefined inclusion criteria. The overall pooled PD-L1 protein positivity rate was 24% (95% CI 15 - 33%) in tumor cells and 33% (95% CI 14 - 56%) in immune cells. PD-L1 protein expression in tumor cells was prognostic for shorter overall survival (HR = 1.63; 95% CI 1.07 - 2.46, p=0.02); there was significant heterogeneity (I2 = 80%, pheterogeneity<0.001). In addition, higher PD-L1 gene expression predicted better survival in multivariate analysis in the entire population (HR=0.82, 95% CI 0.74 - 0.90, p<0.001 for OS) and in basal-like tumors (HR=0.64, 95% CI 0.52 - 0.80, p<0.001 for OS), pinteraction 0.005.CONCLUSION: The largest to our knowledge meta-analysis on the subject informs on PD-L1 protein positivity rates and its prognostic value in breast cancer. Standardization is needed prior to routine implementation. PD-L1 gene expression is a promising prognostic factor, especially in basal-like BC. Discrepant prognostic information might be related to PD-L1 gene expression in the stroma.
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| 3. |
- Öberg, Kjell, et al.
(författare)
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Molecular Pathogenesis of Neuroendocrine Tumors : Implications for Current and Future Therapeutic Approaches
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:11, s. 2842-2849
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Forskningsöversikt (refereegranskat)abstract
- The treatment landscape and biologic understanding of neuroendocrine tumors (NET) has shifted dramatically in recent years. Recent studies have shown that somatostatin analogues have the potential not only to control symptoms of hormone hypersecretion but also have the ability to slow tumor growth in patients with advanced carcinoid. The results of clinical trials have further shown that the VEGF pathway inhibitor sunitinib and the mTOR inhibitor everolimus have efficacy in patients with advanced pancreatic NETs. The efficacy of these targeted therapies in NET suggests that the molecular characterization of NETs may provide an avenue to predict both which patients may benefit most from the treatment and to overcome potential drug resistance. Recent genomic studies of NETs have further suggested that pathways regulating chromatin remodeling and epigenetic modification may play a key role in regulating NET growth. These observations offer the potential for new therapeutic and diagnostic advances for patients with NET.
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