The Role of Adaptive Immunity in the Efficacy of Targeted Cancer Therapies

Xu, Meng; Pu, Yang; Zhang, Yuan; Fu, Yang–Xin

doi:10.1016/j.it.2015.12.007

Cited by 25 publications

(24 citation statements)

References 86 publications

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“…In case of significantly mutated genes (p<0.05), ‘Adaptive immune response’ showed up as significantly enriched pathway in addition to terms ‘GPCR signaling pathway’ and ‘Sensory perception of smell’ (Figure 2c). The role of immune response system players in tumor growth, microenvironment and therapy have been established previously [42,43]. …”

Section: Resultsmentioning

confidence: 99%

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

et al. 2017

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Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and demands effective targeted therapeutic strategies. In this meta-analysis study, we aim to identify significantly mutated genes and regulatory pathways to help us better understand the progression of SCLC and to identify potential biomarkers. Besides ranking genes based on their mutation frequencies, we sought to identify statistically significant mutations in SCLC with the MutSigCV software. Our analysis identified several genes with relatively low mutation frequency, including PTEN, as highly significant (p<0.001), suggesting these genes may play an important role in the progression of SCLC. Our results also indicated mutations in genes involved in the axon guidance pathways likely play an important role in SCLC progression. In addition, we observed that the mutation rate was significantly higher in samples with RB1 gene mutated when compared to samples with wild type RB1, suggesting that RB1 status has significant impact on the mutation profile and disease progression in SCLC.

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Section: Resultsmentioning

confidence: 99%

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

et al. 2017

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“…The BRAF V600E is the most common oncogenic mutation of BRAF in cancer. The mutation results in constitutive activation of the BRAF kinase and promotes cell transformation[87].condensation reaction: in this review's context, is a peptide splicing reaction catalyzed by proteasome, which does not need the initial peptide-bond cleavage (i.e. the step 1 inFig.…”

mentioning

confidence: 99%

Post-Translational Peptide Splicing and T Cell Responses

Mishto

Liepe

2017

Trends in Immunology

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CD8 T cell specificity depends on the recognition of MHC class I-epitope complexes at the cell surface. These epitopes are mainly produced via degradation of proteins by the proteasome, generating fragments of the original sequence. However, it is now clear that proteasomes can produce a significant portion of epitopes by reshuffling the antigen sequence, thus expanding the potential antigenic repertoire. MHC class I-restricted spliced epitopes have been described in tumors and infections, suggesting an unpredicted relevance of these peculiar peptides. We review current knowledge about proteasome-catalyzed peptide splicing (PCPS), the emerging rules governing this process, and the potential implications for our understanding and therapeutic use of CD8 T cells, as well as mechanisms generating other non-canonical antigenic epitopes targeted by the T cell response.

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“…Targeted therapies, such as antibodies against the breast cancer cell receptors HER2 and EGFR, elicit a strong, adaptive immune response, raising the implication that combination immunotherapy with targeted therapy can achieve a synergistic anti-tumour immune response [55,56]. The humanized antibody to VEGF, Avastin (bevacizumab), is FDA-approved for a number of different cancers, and in addition to blocking the pro-angiogenic activity of tumourproduced VEGF, also blocks the immunosuppressive activity of VEGF, which includes suppression of DC maturation [57].…”

Section: Challenge: Design and Identification Of Combination Treatmenmentioning

confidence: 99%

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling

Konstorum

Vella

Adler

et al. 2017

J. R. Soc. Interface.

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The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development.

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The Role of Adaptive Immunity in the Efficacy of Targeted Cancer Therapies

Cited by 25 publications

References 86 publications

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

Significantly mutated genes and regulatory pathways in SCLC—a meta-analysis

Post-Translational Peptide Splicing and T Cell Responses

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling

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