Skip to main content
. 2022 Nov 21;14(22):5720. doi: 10.3390/cancers14225720

Figure 2.

Figure 2

Triangulation of the effects of opioids on pain, immunity and cancer. Cancer can cause pain, by nociceptive, neuropathic, and inflammatory mechanisms, partly caused by the immune response to cancer [1,2,53]. It is this pain state that necessitates opioid use [1,2,49]. Pain is potentially immunosuppressive which might worsen cancer outcomes in some cancer types [44,51,52]. By reducing pain, opioids might have beneficial effects on immune function, the cancer and potentially survival [44,51,52]. However, some opioids suppress immune function, which might decrease anti-tumour immunity and promote cancer growth [6]. Furthermore, there are non-immune effects of opioids on cancer cell regulation [17,18,19,20,28]. Opioids can also act directly on the MOR on cancer and non-cancer cells of the tumour microenvironment [28,30]. Together, these multiple effects converge to influence cancer growth and survival [11,12,54]. The balance of these effects is critical and might be dependent on the immune properties of the opioid used and the cancer type [6,15]. Many of the aforementioned effects are bidirectional (depicted by double arrowed lines in the figure). The immune system, via microglia and cytokines, influences the pain state [55]. Activated immune cells can also produce endogenous opioids, as well as morphine [56]. The immune system and the cancer are constantly influencing each other, with processes such as immunoediting and immunosculpting [57]. The aforementioned interactions lead to either cancer cell destruction or growth. How the cancer progresses influences survival. Green arrows depict a beneficial effect, red arrows depict a detrimental effect of opioids on the immune system, cancer development and survival. Question marks are used to highlight uncertainly of the net balance of effects, which might vary depending on the opioid. Adapted with permission from Boland, J.W. et al. Br. J. Pharmacol. 2018, 175, 2726–2736. [15]; Boland, J.W. et al. Br. J. Cancer 2014, 111, 866–873 [22]; Eur. J. Clin. Pharmacol. 2020, 76, 393–402. [12].