Comparative Approach to the Temporo-Spatial Organization of the Tumor Microenvironment

Abstract

The complex ecosystem in which tumor cells reside and interact, termed the tumor microenvironment (TME), encompasses all cells and components associated with a neoplasm that are not transformed cells. Interactions between tumor cells and the TME are complex and fluid, with each facet coercing the other, largely, into promoting tumor progression. While the TME in humans is relatively well-described, a compilation and comparison of the TME in our canine counterparts has not yet been described. As is the case in humans, dog tumors exhibit greater heterogeneity than what is appreciated in laboratory animal models, although the current level of knowledge on similarities and differences in the TME between dogs and humans, and the practical implications of that information, require further investigation. This review summarizes some of the complexities of the human and mouse TME and interjects with what is known in the dog, relaying the information in the context of the temporo-spatial organization of the TME. To the authors' knowledge, the development of the TME over space and time has not been widely discussed, and a comprehensive review of the canine TME has not been done. The specific topics covered in this review include cellular invasion and interactions within the TME, metabolic derangements in the TME and vascular invasion, and the involvement of the TME in tumor spread and metastasis.

The ferroptosis signature predicts the prognosis and immune microenvironment of nasopharyngeal carcinoma

“…The tumor microenvironment (TME) is a unique environment with infiltrating immune and nonimmune cells 44 . Immune components can modulate the occurrence and development of cancers in the TME [45][46][47] . In this study, functional enrichment analyses demonstrated that the risk model was involved in immune-based pathways.…”

Translating energy balance research from the bench to the clinic to the community: Parallel animal‐human studies in cancer

“…Their complex tumor microenvironment similarly influences recurrence, metastasis, and treatment resistance. 31,32 Because standards of care do not exist in many canine cancers, it is possible to initiate phase 0, 1, and 2 trials before other treatments. 33 Cancer development and progression occur at faster rates in dogs, allowing for shorter, less costly, yet relevant clinical trials.…”

“…Like humans, companion‐animal models allow for the incorporation of aging and comorbidities in an immunocompetent host. Their complex tumor microenvironment similarly influences recurrence, metastasis, and treatment resistance 31,32 . Because standards of care do not exist in many canine cancers, it is possible to initiate phase 0, 1, and 2 trials before other treatments 33 .…”

Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?

“…A further requirement for cancer formation is that the transformed cells must have a permissive environment where they can grow and develop the complex anatomical structures that create tumors. [54][55][56] Recently, Laconi and colleagues proposed that, "the tumor-suppressive potential of youth is more potent than previously realized, limiting cancers through half a century of human life even in the face of increased DNA mutations and highly perturbed tissue environments," 57 and much additional work suggests that organismal aging and the associated development of cellular senescence, proinflammation, and waning immunity appear to be major mechanisms that allow for the development of these permissive environments. [58][59][60][61][62][63][64] Pathologically significant mutations are propagated during the process of DNA replication, as nondividing cells will not pass on the cancer phenotype to progeny cells.…”