Cross‐talk between tumors at anatomically distinct sites

Abstract

Cancer tissue is not homogenous, and individual metastases at different anatomical locations can differ from the primary tumor and from one another in both their morphology and cellular composition, even within an individual patient. Tumors are composed of cancer cells and a range of other cell types, which, together with a variety of secreted molecules, collectively comprise the tumor microenvironment (TME). Cells of the TME can communicate with each other and with distant tissues in a form of molecular cross‐talk to influence their growth and function. Cross‐talk between cancer cells and local immune cells is well described and can lead to the induction of local immunosuppression. Recently, it has become apparent that tumors located remotely from each other, can engage in cross‐talk that can influence their responsiveness to various therapies, including immunotherapy. In this article, we review studies that describe how tumors systemically communicate with distant tissues through motile cells, extracellular vesicles, and secreted molecules that can affect their function. In addition, we summarize evidence from mouse studies and the clinic that indicate an ability of some tumors to influence the progression and therapeutic responses of other tumors in different anatomical locations.

Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer

“…The tumor microenvironment (TME) is composed of different infiltrating host cells and different molecules that are secreted from cancer cells [ 19 , 20 ]. One mechanism that tumor cells use that is well characterized is the programmed cell death protein 1 (PD-1)/PD-ligand (PD-L) pathway.…”

Primary and metastatic breast tumors cross-talk to influence immunotherapy responses

“… 13 – 15 In metastatic disease, these tumors are linked through the blood and lymphatic circulatory networks. 5 Despite evidence in specific contexts, such as abscopal responses and the pre-metastatic niche, there is limited research into how distal tumors in various anatomical sites influence each other. 2 , 3 , 5 Here, we utilized murine models of cancer to investigate the consequences to immunotherapy responses in mice bearing tumors with discrepant TMEs and immunotherapeutic outcomes.…”

“…These changes are mediated by circulating factors including growth factors, tumor-derived extracellular vesicles, and immune cell populations that are propagated by the tumor cells and TME. [5][6][7][8][9] Systemic and distant influences of localized tumors are evidenced by studies of the pre-metastatic niche and abscopal effect of local radiation. 2,3 Secreted and cellular factors from the primary tumor influence the pre-metastatic tissue to create an environment conducive for tumor establishment.…”

“… 1 Systemic immune responses against tumors have been shown to impact distal tissues and tumors through the lymphatics and vascular systems. 2 – 5 Tumor cells and the surrounding tumor microenvironment (TME) in one metastatic lesion have the potential to influence the TME composition in distant tumors. These changes are mediated by circulating factors including growth factors, tumor-derived extracellular vesicles, and immune cell populations that are propagated by the tumor cells and TME.…”

“…These changes are mediated by circulating factors including growth factors, tumor-derived extracellular vesicles, and immune cell populations that are propagated by the tumor cells and TME. 5 – 9 …”