Tumorigenesis: it takes a village

Tabassum, Doris P.; Polyák, Kornélia

doi:10.1038/nrc3971

Cited by 496 publications

(479 citation statements)

References 83 publications

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“…Consequently, several studies have started to focus on the ecological cooperation or competitive interactions between tumor populations (Merlo et al 2006;Moreno 2008;Neelakantan et al 2015;Tabassum and Polyak 2015). In primary breast tumors, recent research using mouse models has characterized the polyclonal origin of certain tumor types and the interclonal cooperation between multiple subclones (Cleary et al 2014).…”

Section: Clonal Cooperationmentioning

confidence: 99%

Distinctive properties of metastasis-initiating cells

2016

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Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies.

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Section: Clonal Cooperationmentioning

confidence: 99%

Distinctive properties of metastasis-initiating cells

2016

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“…Advanced carcinomas are composed of multiple subclones that, despite a common cellular origin and shared founder mutations, show divergent genetic, biologic, clinical, and immunologic properties (1). Moreover, the subclonal structure of cancers continually evolves in response to the selective pressures imposed by the host and the cytotoxic effects of treatment (2).…”

Section: Introductionmentioning

confidence: 99%

Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer

Kroeger

Milne

Nelson

2016

Clinical Cancer Research

437

335

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Purpose: CD8+ tumor-infiltrating lymphocytes (TIL) are key mediators of antitumor immunity and are strongly associated with survival in virtually all solid tumors. However, the prognostic effect of CD8+ TIL is markedly higher in the presence of CD20+ B cells, suggesting that cooperative interactions between these lymphocyte subsets lead to more potent antitumor immunity. Experimental Design: We assessed the colocalization patterns, phenotypes, and gene expression profiles of tumor-associated T- and B-lineage cells in high-grade serous ovarian cancer (HGSC) by multicolor IHC, flow cytometry, and bioinformatic analysis of gene expression data from The Cancer Genome Atlas. Results: T cells and B cells colocalized in four types of lymphoid aggregate, ranging from small, diffuse clusters to large, well-organized tertiary lymphoid structures (TLS) resembling activated lymph nodes. TLS were frequently surrounded by dense infiltrates of plasma cells (PC), which comprised up to 90% of tumor stroma. PCs expressed mature, oligoclonal IgG transcripts, indicative of antigen-specific responses. PCs were associated with the highest levels of CD8+, CD4+, and CD20+ TIL, as well as numerous cytotoxicity-related gene products. CD8+ TIL carried prognostic benefit only in the presence of PCs and these other TIL subsets. PCs were independent of mutation load, BRCA1/2 status, and differentiation antigens but positively associated with cancer–testis antigens. Conclusions: PCs are associated with the most robust, prognostically favorable CD8+ TIL responses in HGSC. We propose that TLS facilitate coordinated antitumor responses involving the combined actions of cytolytic T cells and antibody-producing PCs. Clin Cancer Res; 22(12); 3005–15. ©2016 AACR.

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“…Tumor heterogeneity and acquired resistance to treatment via the emergence and growth of resistant tumor cell subpopulations is one of the major challenges facing the field of cancer therapeutics (46). Assessment of the state of heterogeneity within individual tumors and temporal dynamics of tumor evolution have become very important in one's understanding of tumor pathogenesis as well as in monitoring tumor evolution as a function of therapy (47).…”

Section: Tumor Heterogeneitymentioning

confidence: 99%

Challenging Roadblocks to Cancer Cure

Loda

2016

Cancer Research

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The Pezcoller Symposium in Trento, Italy, June 2015, focused entirely on the question of why advanced cancer cure is so uncommon despite the extraordinarily rapid growth of invaluable therapeutic information. Participants were asked to define and to critically evaluate real and potential obstacles to permanent disease eradication. High-level concepts on potential road blocks to cures as well as opportunities for intervention in diverse areas of investigation ranging from genomic alterations to metabolism, microenvironment, immunity, and mechanotransduction were discussed. Provocative concepts and novel therapeutic avenues were proposed. What follows is a critical analysis of the highlights of this meeting. Cancer Res; 76(17); 4924-30. Ó2016 AACR.

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Tumorigenesis: it takes a village

Cited by 496 publications

References 83 publications

Distinctive properties of metastasis-initiating cells

Distinctive properties of metastasis-initiating cells

Tumor-Infiltrating Plasma Cells Are Associated with Tertiary Lymphoid Structures, Cytolytic T-Cell Responses, and Superior Prognosis in Ovarian Cancer

Challenging Roadblocks to Cancer Cure

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