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Tumor Discovery Cell-cell communication in cancer

and an influx of immunosuppressive myeloid cells, immune cells, vascular endothelial cells, and mesenchymal
which release reactive oxygen species, pro-inflammatory cells (Figure 3). This communication significantly impacts
cytokines, chemokines, and angiogenic factors. These tumor biological activities such as immune regulation,
mediators drive tissue damage, DNA mutations, vascular angiogenesis, and EMT, which in turn influence tumor cell
dysfunction, and matrix remodeling—processes growth, proliferation, and metastasis. 22
that fuel tumor initiation and progression. Classic Emerging research underscores exosomes as dynamic
16
examples include inflammatory bowel disease (linked to mediators of intercellular communication, facilitating the
colorectal cancer), chronic hepatitis or fatty liver disease transfer of proteins, mRNAs, miRNAs, and oncoproteins
(associated with hepatocellular carcinoma), and asbestos- to recipient cells. These cargo molecules modulate
23
induced inflammation (a precursor to mesothelioma). diverse processes such as immunoregulation, extracellular
Obesity-related inflammation similarly elevates risk for matrix remodeling, and growth factor signaling, which
malignancies such as breast and endometrial cancers. 17
collectively influence tumor progression. Within the
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Whether tumors arise from pre-existing inflammation TME—a network of tumor-associated fibroblasts, immune
or trigger inflammation during early growth, most cells, and osteoblasts—exosomes play multiple roles: they
cancers share mechanisms to evade immune surveillance. enhance tumor cell proliferation, confer chemotherapy
Progressing tumors frequently exclude or impair anti-tumor resistance, and regulate stromal cell behavior. Stromal cells
immune cells (T cells, natural killer cells, and dendritic in the TME internalize exosomal miRNAs, mRNAs, and
cells) while recruiting pro-tumor myeloid populations proteins, which subsequently orchestrate pro-tumorigenic
like macrophages and neutrophils. 18,19 This dual strategy signaling cascades. 25
fosters an immunosuppressive, pro-angiogenic niche that
supports tumor survival and spread. Targeting tumor-derived exosomes may positively
impact cancer therapy. Exosomes secreted by malignant
4. Long-range cell communication via cells have a tumor-promoting effect, and tumor cells
tumor exosomes generally secrete more exosomes than normal cells.
These secretomes carry mRNA, miRNAs, lncRNAs, and
Exosomes are extracellular vesicles ranging from 30 proteins that can serve as biomarkers for cancer diagnosis
to 150 nm in diameter, released by various cell types, and prognostic monitoring. In addition, exosomes play
26
including tumor cells. They can induce apoptosis, modulate a crucial role in therapy resistance. They carry specific
the immune system, and serve as biomarkers for diagnosis. payloads that can transfer resistant phenotypes to sensitive
As a crucial component of cell-to-cell communication, cancer cells, conferring resistance to chemotherapy and
exosomes regulate the TME and are involved in the radiation by altering the cell cycle and inducing anti-
development, progression, and metastasis of numerous apoptotic processes. Exosomes may also inhibit the entry of
cancers. 20,21 chemotherapeutic agents into target cancer cells, affecting
21
Tumor-derived exosomes contain proteins, nucleic the efficacy of chemotherapy. Therefore, targeting tumor
acids, lipids, and metabolites that act as effective messengers exosomes may offer a new direction for cancer therapy,
between tumor cells and various other cells, including and relevant clinical trials are already underway.

Figure 3. Exosomes mediate cell–cell communication locally and systemically. When reaching the recipient cell, tumor-derived donor exosomes can either
trigger signaling by directly interacting with extracellular receptors or be uptaken by direct fusion with the plasma membrane and get internalized. The
figure was created with BioRender.com.

Volume 4 Issue 2 (2025) 95 doi: 10.36922/td.8323