Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis

Turajlic, Samra; Litchfield, Kevin; Xu, Hang; Rosenthal, Rachel; McGranahan, Nicholas; Reading, James L.; Wong, Yien Ning Sophia; Rowan, Andrew; Kanu, Nnennaya; Bakir, Maise Al; Chambers, Tim; Salgado, Roberto; Savas, Peter; Loi, Sherene; Birkbak, Nicolai J.; Sansregret, Laurent; Gore, Martin; Larkin, James; Quezada, Sergio A.; Swanton, Charles

doi:10.1016/s1470-2045(17)30516-8

Cited by 789 publications

(721 citation statements)

References 73 publications

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“…[1][2][3][4][5][6][7] Based on the available data, it is clear that ICD can facilitate T cell responses against a wide-spectrum of differentiation, over-expressed, and mutated tumor-associated antigens (TAAs). [1][2][3][4][8][9][10][11][12][13] However, the predominance of a fraction of TAA-specific T cells in driving ICD-based immunity might be regulated by: (1) the spatiotemporal expression patterns of specific TAAs within a tumor, [14][15][16][17][18][19][20] (2) the overall coverage of various TAAs by central or peripheral tolerance, [21][22][23] (3) the overall avidity of the T cell receptor (TCR) for specific TAA, [24][25][26][27][28][29][30][31][32] and (4) the general cellular and metabolic health of effector or memory T cell fractions. [33][34][35][36][37][38] Operationally, two experimental procedures have been established over the years to identify bona fide ICD inducers in vivo.…”

Section: Introductionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

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Section: Introductionmentioning

confidence: 99%

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

et al. 2017

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“…Tumor mutational burden is thought to be associated with an increase of neo‐antigens that leads to the enhancement of recognition by the immune system . The analysis of pan‐cancer somatic mutation data obtained from The Cancer Genome Atlas for whole‐exon sequencing data from 19 kinds of cancers including 5777 solid tumors showed that ccRCC had the highest proportion of coding insertions and deletions, and papillary RCC and chromophobe RCC had the second and third highest proportion …”

Section: Biomarkers For Immune Checkpoint Therapymentioning

confidence: 99%

Current status of prognostic factors in patients with metastatic renal cell carcinoma

et al. 2019

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In recent years, the induction of novel agents, including molecular‐targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.

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“…For this discrepancy, Turajlic et al . reported that RCC showed the highest proportion and number of insertion and deletion mutations (indels) . Most studies about the correlation between the effect of ICI and TMB focus on SNVs.…”

Section: Biomarkers For Immunotherapymentioning

confidence: 99%

Immunotherapy for genitourinary tumors

Nakayama

Kitano

2019

Int J of Urology

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The present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin‐2 and interferon‐alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed.

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Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis

Cited by 789 publications

References 73 publications

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics

Current status of prognostic factors in patients with metastatic renal cell carcinoma

Immunotherapy for genitourinary tumors

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