The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process

Wu, Chung‐I; Wang, Hurng‐Yi; Ling, Shaoping; Lu, Xuemei

doi:10.1146/annurev-genet-112414-054842

Cited by 91 publications

(100 citation statements)

References 149 publications

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“…Although genetic instability is not a requirement for cancer development (10), cancers exhibit a mutator phenotype (11), which results in the often remarkable heterogeneity of cancers (12). Genetic instability allows cancer cells to develop resistance to all kind of therapies.…”

Section: Introductionmentioning

confidence: 99%

Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1–Resistant Tumors Leading to Tumor Eradication

Arina

Karrison

Galka

et al. 2017

Cancer Immunology Research

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Adoptively transferred CD8+ T cells can stabilize the size of solid tumors over long periods of time by exclusively recognizing antigen cross-presented on tumor stroma. However, these tumors eventually escape T cell–mediated growth control. The aim of this study was to eradicate such persistent cancers. In our model, the SIYRYYGL antigen is expressed by cancer cells that lack the MHC-I molecule Kb needed for direct presentation, but the antigen is picked up and cross-presented by tumor stroma. A single injection of antigen-specific 2C CD8+ T cells caused long-term inhibition of tumor growth, but without further intervention, tumors started to progress after approximately 3 months. Escape was associated with reduced numbers of circulating 2C cells. Tumor-infiltrating 2C cells produced significantly less TNFα and expressed more of the “exhaustion” markers PD-1 and Tim-3 than T cells from lymphoid organs. High-dose local ionizing radiation, depletion of myeloid-derived suppressor cells, infusions of additional 2C cells, and antibodies blocking PD-L1 did not prevent tumor escape. In contrast, adoptive transfer of allogeneic CD4+ T cells restored the numbers of circulating Ag-specific CD8+ T cells and their intratumoral function, resulting in tumor eradication. These CD4+ T cells had no antitumor effects in the absence of CD8+ T cells and recognized the alloantigen cross-presented on tumor stroma. CD4+ T cells might also be effective in cancer patients when PD1/PD-L1 blockade does not rescue intratumoral CD8+ T-cell function and tumors persist.

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Section: Introductionmentioning

confidence: 99%

Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1–Resistant Tumors Leading to Tumor Eradication

Arina

Karrison

Galka

et al. 2017

Cancer Immunology Research

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“…We shall present the analysis of somatic mutations first. 1) Fitness-altering mutations in the soma leading to tumorigenesis -A mutation is assumed to affect fitness with probability r. Based on the analysis of 299 cancer driver genes (Bailey, et al 2018), we set r at 0.04 (See Methods; (Wu, et al 2016)). The number of genetic events needed to start tumorigenesis has been estimated to be 5 -10 (Fearon and Vogelstein 1990;Hanahan and Weinberg 2011).…”

Section: Fitness-altering Mutationsmentioning

confidence: 99%

“…Beyond driver and neutral (passenger) mutations, the existence of deleterious mutations in tumors has been controversial (Wu, et al 2016;Zapata, et al 2018). Such mutations presumably could slow down cancer evolution and should be relevant only when data on non-cancerous clonal expansions are included (see Chen, Ruan et al, unpublished results).…”

Section: Fitness-altering Mutationsmentioning

confidence: 99%

Mutations beget more mutations – The baseline mutation rate and runaway accumulation

Ruan

Chen

et al. 2019

Preprint

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There is a sizable literature on mutation rate evolution (Drake 1991;Makova and Li 2002;Lynch 2011;Scally and Durbin 2012;Sung, et al. 2012) but few studies incorporate the recent genomic data from somatic tissues that suggest the operation of mutators. These data show that the mutation burden among cancer samples may vary by several orders of magnitude (Kandoth, et al. 2013;Lawrence, et al. 2013). We now propose a runaway model, applicable to both the germline and the soma, whereby the accumulation of mutator mutations forms a positive-feedback loop. In this loop, any mutator mutation would increase the probability of acquiring the next mutator, thus triggering a runaway escalation in mutation rate. The process can be initiated more readily if there are many weak, rather than a few strong, mutators. Interestingly, even a small increase in the mutation rate at birth could trigger the runaway process, resulting in unfit progeny in slowly reproducing species. In such species, the need to minimize the risk of this uncontrolled accumulation would entail a mutation rate that may seem unnecessarily low. In comparison, species that starts and ends reproduction much sooner do not face the risk and may set the baseline mutation rate higher. The mutation rate would evolve as the generation time changes, therefore explaining many puzzling evolutionary phenomena (Elango, et al.

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“…Given the complete genomic linkage of asexually reproducing populations (due to the lack of recombination) such as tumor cells, interference between positive and negative selection (known as the Hill-Robertson effect) [230] may be particularly strong when accompanied by high mutation rates [231]. Intriguingly, McFarland et al [232, 233] found that deleterious mutations significantly alter tumor progression by impeding the efficiency of positive selection.…”

Section: Evolutionary Forces Determining the Extent Of Genetic Hetmentioning

confidence: 99%

A population genetics perspective on the determinants of intra-tumor heterogeneity

Sun

Curtis

2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Cancer results from the acquisition of somatic alterations in a microevolutionary process that typically occurs over many years, much of which is occult. Understanding the evolutionary dynamics that are operative at different stages of progression in individual tumors might inform the earlier detection, diagnosis, and treatment of cancer. Although these processes cannot be directly observed, the resultant spatiotemporal patterns of genetic variation amongst tumor cells encode their evolutionary histories. Such intra-tumor heterogeneity is pervasive not only at the genomic level, but also at the transcriptomic, phenotypic, and cellular levels. Given the implications for precision medicine, the accurate quantification of heterogeneity within and between tumors has become a major focus of current research. In this review, we provide a population genetics perspective on the determinants of intra-tumor heterogeneity and approaches to quantify genetic diversity. We summarize evidence for different modes of evolution based on recent cancer genome sequencing studies and discuss emerging evolutionary strategies to therapeutically exploit tumor heterogeneity.

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The Ecology and Evolution of Cancer: The Ultra-Microevolutionary Process

Cited by 91 publications

References 149 publications

Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1–Resistant Tumors Leading to Tumor Eradication

Transfer of Allogeneic CD4+ T Cells Rescues CD8+ T Cells in Anti-PD-L1–Resistant Tumors Leading to Tumor Eradication

Mutations beget more mutations – The baseline mutation rate and runaway accumulation

A population genetics perspective on the determinants of intra-tumor heterogeneity

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