Tumor microenvironment and macroenvironment: A new perspective on holistic oncology

Area of Science:

• Oncology
• Cancer Biology
• Immunology

Background:

• The tumor microenvironment (TME) and tumor macroenvironment (TMaE) are critical determinants of cancer initiation, progression, and therapeutic resistance.
• The TME encompasses local cellular niches, while the TMaE integrates systemic signals like metabolism, immunity, and inflammation.
• Current models inadequately represent the complex interplay between local and systemic factors in cancer.

Purpose of the Study:

• To review the distinct and overlapping roles of the TME and TMaE in shaping cancer biology.
• To highlight the mechanisms through which systemic factors influence local tumor ecosystems.
• To emphasize the need for integrated models to understand local-systemic crosstalk in cancer.

Main Methods:

• Literature review of recent advances in cancer biology, focusing on TME and TMaE interactions.
• Analysis of how systemic physiological factors impact tumor progression and treatment response.
• Discussion of current limitations in conceptualizing and modeling TME-TMaE crosstalk.

Main Results:

• Both TME and TMaE are integral to tumor initiation, progression, dormancy, and metastasis.
• Systemic factors (aging, metabolic imbalance, inflammation, stress) significantly remodel the TME and influence cancer outcomes.
• The interaction between local tumor niches and systemic physiology is complex and bidirectional.

Conclusions:

• A comprehensive understanding of TME-TMaE interactions is essential for refining precision oncology and preventive strategies.
• Future research should integrate multi-omics, advanced imaging, and humanized models to elucidate local-systemic crosstalk.
• Targeting both local and systemic cancer ecosystems offers a promising avenue for combinatorial therapies.