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| Component | Function | Classification |
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| Cancer-associated fibroblasts (CAFs) | Sustaining proliferative signaling; activating angiogenesis and metastasis; tumor-promoting inflammation; evading immune destruction; reprograming cellular metabolism; promoting genome instability and mutation. | Tumor promoting; less known of tumor inhibiting; abundant in TME; commonly used markers including α-SMA, FAP-α, FSP-1/S100A4, and PDGFRβ; the origin of CAFs is not clear, and CAFs can differentiate stimulation by ROS and TGF-β1-dependent and TGF-β1-independent mechanisms. |
| Immune cells | | |
| Neutrophils | Enhancement of angiogenesis and metastasis; associated with poor prognosis. | Tumor promoting (N2); tumor inhibiting (N1); increased levels in the colon, stomach, and lung cancer patients. |
| Tumor-associated macrophages (TAMs) | Promoting degradation of the extracellular matrix; aiding the expansion of inflammatory cytokines, such as TNF-β; enhancement of angiogenesis and remodeling. | Tumor promoting (M2); tumor inhibiting (M1); the major protumoral component in TME; the first nonneoplastic cells infiltrating the tumor; attracted by chemokines secreted by both malignant and stromal cells. |
| CD8+ cytotoxic T cells (CTL) | Induce apoptosis, necrosis, and growth arrest by releasing INF-γ and other cytotoxic cytokines; establishing an antitumor environment. | Tumor inhibiting; the major antitumoral component in TME. |
| Regulatory T cells (Tregs) | Secreting cytokines such as IL-10, TGF-β; establishing an immunosuppressive environment; associated with poor prognosis. | Tumor promoting; promoting tumor maintenance. |
| Myeloid-derived suppressor cells (MDSCs) | Associated with tumor progression and neoangiogenesis; suppressing T cells and NK cells; differentiating into TAMs under hypoxic conditions. | Tumor promoting; increased in almost all patients/animals with cancer; including premature granulocytes, macrophages, dendritic cells, and myeloid precursors. |
| Mesenchymal stem cells (MSCs) | Differentiating into mesenchymal tissues such as bone, cartilage, and fat tissues, vasculogenic mimicry; forming the premetastatic niche; promoting cancer initiation and malignancy. | Tumor promoting; the major component of stromal cells in TME. |
| Endothelial cells | Consisting of tumor blood vessels; secreting angiocrine factors such as adhesion molecules; intercommunicating with tumor cells via secreting EVs including CD106, CD49a. | Tumor promoting. |
| Adipocytes | Regulating the balance of systematic energy and metabolism; secreting exosomes, cytokines, chemokines, and hormones; promoting cancer progression. | Tumor promoting. |
| Neuroendocrine cells (NE cells) | Promoting proliferative signaling; secreting neurotransmitters, including CgA, chromophilic and vasoactive polypeptide; regulating NK cell migration and toxicity ability. | Tumor promoting. |
| Vascular network | Providing oxygen, clearing carbon dioxide, and metabolizing wastes; providing nutrition support for cancer cells; promoting angiogenesis and metastasis. | Tumor promoting; all malignant tumors are angiogenesis-dependent. |
| Lymph vessels | Helping immune cell avoid immunity and dissemination; providing a physical link between lymph nodes and tumor. | Tumor promoting. |
| Extracellular vesicles (EVs) | Carrying biologically active molecules such as proteins, miRNAs, and lncRNAs from donor cell to recipient cell; regulating key signaling pathways, proliferation, drug resistance, and stemness; reprogramming stromal cells to create a niche for survival. | Tumor promoting; tumor inhibiting; membrane-wrapped vesicles including exosomes, microvesicles, and apoptotic bodies; as a critical mediator between tumor and the TME. |
| Extracellular matrix (ECM) | Forming the complex macromolecular network; controlling cancer invasion and metastasis, angiogenesis; contribution to growth and proliferation signaling, inhibiting cancer apoptosis. | Tumor promoting; a noncellular three-dimensional network including collagen, elastin, fibronectin, proteoglycans, laminins, and glycoproteins. |
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