Опухоль-промотирующее воспаление | ПРЕЦИЗИОННАЯ ОНКОЛОГИЯ

Опухоль-промотирующее воспаление

Douglas Hanahan, Robert A. Weinberg. Hallmarks of cancer: the next generation. Cell, Volume 144, Issue 5, p646–674, 4 March 2011


Pathologists have long recognized that some tumors are densely infiltrated by cells of both the innate and adaptive arms of the immune system and thereby mirror inflammatory conditions arising in non-neoplastic tissues. With the advent of better markers for accurately identifying the distinct cell types of the immune system, it is now clear that virtually every neoplastic lesion contains immune cells present at densities ranging from subtle infiltrations detectable only with cell type-specific antibodies to gross inflammations that are apparent even by standard histochemical staining techniques. Historically, such immune responses were largely thought to reflect an attempt by the immune system to eradicate tumors, and indeed, there is increasing evidence for antitumoral responses to many tumor types with an attendant pressure on the tumor to evade immune destruction, as discussed below.

By 2000, there were already clues that the tumor-associated inflammatory response had the unanticipated, paradoxical effect of enhancing tumorigenesis and progression, in effect helping incipient neoplasias to acquire hallmark capabilities. In the ensuing decade, research on the intersections between inflammation and cancer pathogenesis has blossomed, producing abundant and compelling demonstrations of the functionally important tumor-promoting effects that immune cells—largely of the innate immune system—have on neoplastic progression. Inflammation can contribute to multiple hallmark capabilities by supplying bioactive molecules to the tumor microenvironment, including growth factors that sustain proliferative signaling, survival factors that limit cell death, proangiogenic factors, extracellular matrix-modifying enzymes that facilitate angiogenesis, invasion, and metastasis, and inductive signals that lead to activation of EMT and other hallmark-facilitating programs.

Importantly, inflammation is in some cases evident at the earliest stages of neoplastic progression and is demonstrably capable of fostering the development of incipient neoplasias into full-blown cancers. Additionally, inflammatory cells can release chemicals, notably reactive oxygen species, that are actively mutagenic for nearby cancer cells, accelerating their genetic evolution toward states of heightened malignancy. As such, inflammation can be considered an enabling characteristic for its contributions to the acquisition of core hallmark capabilities. The cells responsible for this enabling characteristic are described in the section below on the tumor microenvironment.

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