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Table 2 Immune reactions in cancer and biofilm infection

From: Immunometabolism in biofilm infection: lessons from cancer

Immune reaction Cancer Biofilm
Polymorphonuclear leukocytes (PMNs) Cancer cells, via release chemokines, recruit neutrophils called tumor-associated neutrophils (TANs) with functions, including pro-and anti-cancer effects. Also, TANs can generate many agents that contribute to tumor growth, metastasis, and angiogenesis, including cathepsins, pro-angiogenic cytokines, and Matrix metalloproteinases (MMPs) (Masucci et al. 2019)
Activated PMNs appear to affect cancer progression by their immunosuppressive effects and inhibition of T-cell functions (Schmielau and Finn 2001)
PMN appears to be significantly involved in initiating and enhancing angiogenesis and tumor metastasis in patients with oral cancer (Jablonska et al. 2002)
Unexpected antitumor effects associated with long-term employment of granulocyte colony-stimulating factor, which induces severe and persistent neutrophil stimulation, have been an easy method for solid tumors to encourage severe peritumoral PMN in tumor Sections (Souto et al. 2011)
PMN-MDSCs have immunosuppressive activity and restrict immune activity in the tumor, recurrent infectious conditions, trauma, sepsis, and many pathological diseases (2018)
Neutrophils, similar to macrophages, have two phenotypes, including N1 and N2, which have anti-tumor/anti-inflammatory and pro-tumor/inflammatory effects, respectively (Zhu et al. 2015; Genard et al. 2018; Fridlender et al. 2009). Although they are phenotypically different, to date, no marker is available to differentiate the phenotype of N1 from N2 in the tumor micro-environment. Reactive oxygen species (ROS) production in the N2 phenotype is very high, contributing to tumor progression in various directions (Injarabian et al. 2019)
The small contribution of PMNs to the immune response during S. aureus biofilm infection indicates that biofilms also circumvent significant PMN uptake by the currently unknown mechanisms (Heim et al. 2014, 2015; Hanke et al. 2013)
Lysed PMN cells increase biofilm production in P. aeruginosa strains (Walker et al. 2005; Parks et al. 2009)
When P. aeruginosa biofilms were formed together with PMN cells in vitro, the PMN localized to the biofilm surface but had very little microbicidal activity (Maurice et al. 2018; Rasamiravak et al. 2015)
It has been found that P. aeruginosa utilizes PMN in a diabetic mouse model for bacterial wound infections (Watters et al. 2014)
Macrophage One of the most abounding cells in solid tumors' environment in macrophages, these cells' presence in cancer is correlated with reduced patient survival Nielsen SR and Schmid (2017)
Tumor-associated macrophage (TAMs) promotes cancer metastases via various pathways such as facilitating angiogenesis, stimulating tumor formation, and enhancing tumor cell migration and invasion (Dandekar et al. 2011)
Macrophage activated by breast cancer cells has contributed to TNF-dependent stimulation of nuclear factor-B signaling pathways and c-Jun-NH2-kinase in cancer cells (Dunn et al. 2004)
Macrophages exhibit several protumorigenic functions that play an essential role in cancer development and progression, such as producing cytokines and inducing tumor angiogenesis (Grivennikov et al. 2010)
Macrophages enhance aggression and metastases from the primary cancer cells by their ability to join tumor cells in an autocrylic ring that promotes tumor cell migration (Wyckoff et al. 2007; Wyckoff et al. 2004)
Biofilms polarize macrophages towards anti-inflammatory phenotypes by decreasing pro-inflammatory reactions and restricting macrophages' in vivo invasion (Hanke et al. 2013; Sadowska et al. 2013)
The proteinaceous factors produced by S. aureus (biofilm-producing) can restrain macrophage phagocytosis (2015)
Macrophage dysfunction caused by S. aureus biofilm is partially dependent on agr (2015)
Macrophages profile differential gene it has been found toward S. aureus biofilms (Scherr et al. 2013)
Biofilm-activated M1-macrophages show that they can control biofilm infections (Yu et al. 2020)
T helper type 1 (Th1) cells Clinical findings show that Th1/Th2 imbalances have been identified with elevated cytokines produced by Th2 in breast cancer patients (Xu 2014)
Patients with a dominant Th1 response have been shown to have higher survival and lower cancer recurrence rates (Zhao et al. 2019)
Changes in the response from Th1 to Th2 promote the development of breast cancer (Sherene et al. 2013)
Cancer eradication is achieved by the cooperation of tumor-specific Th1 cells and tumor-penetrating antigen macrophages (Haabeth et al. 2011)
Inflammation, when stimulated by tumor-specific Th1 cells, may kill cancer cells (Haabeth et al. 2011)
Many immune modulators can increase the production of Th1 cytokines and boost Th1 immunity in response to cancer vaccines (Xu 2014)
An early pro-inflammatory response to Th1 and Th17, together with a down-regulated Th2 response, has been shown to arise in the initial phases of biofilm infections and may trigger tissue injury that helps S. aureus to be connected to and grown as a biofilm (Shirtliff et al. 2002)
Biofilms indue the occurrence of CD80 and CD86, which also stimulate Th1 and Th2, respectively, suggesting the importance of a skew in the T-cell response (Slavik et al. 1999)
Th1 responses may be unsuccessful in removing S. aureus at reduced oxygen partial pressure in the biofilm's depth (Shirtliff et al. 2002)
Biofilms have been correlated with Th1 skewing in acquired immunity, while biofilm species have not been established (González et al. 2018)
T helper type 2 (Th2) cells Th2 cells create Interleukin-4 (IL-4), and interleukin-10 (IL-10) supports tumor development by impairing the human immune response (Zhao et al. 2019)
Compared to the Th1 response, the Th2 response could help cancer development (Narsale et al. 2018)
The inability of Th2 cells to destroy primary cancer cells appears to be due to IL-2 deficiency, which does not allow the production of a specific anti-tumor Cytotoxic T lymphocyte (CTL) reaction (Bass et al. 1993; Erard et al. 1993)
CD4 + Th2 cells mediated the tumor-suppressive effect of the thymic stromal lymphopoietin (TSLP) in these models of skin carcinogenesis (Protti 2020)
Th2 responses are effective in removing biofilm illnesses during the initial stages of biofilm growth (Shkreta et al. 2004)
It was shown that in 53 Chronic rhinosinusitis patients, S. aureus biofilms were correlated with Th2 skewing from the acquired immune response (Foreman et al. 2011)
Recent data suggest a protective role for Th2/Treg anti-inflammatory cells, as pro-inflammatory Th1/Th17 signaling, in the early development of S. aureus biofilm (Prabhakara et al. 2011)
CD8 T cells Higher levels of CD8 + T cells are significantly associated with the specific survival of breast cancer (Mahmoud 2011)
CD8+ T cells and CD4+ T cells were shown to have anti-tumor effects, while regulatory T cells (CD4+ CD25+ Tregs) could be accountable for the immunological hyporesponsiveness found in cancer (Sutmuller et al. 2001; Shimizu et al. 1999)
In human cancer, CTL infiltration has been linked with improved clinical results and longevity in melanoma, ovarian cancer, and colon cancer Camus and Galon (2010)
Not determined
Dendritic cells Dendritic cells (DCs) are recognized as critical players in cancer control by adaptive immunity Hansen et al. (2017)
When the tumor grows early or late, depletion DCs have opposite tumor progression consequences (Scarlett et al. 2012)
Only CD103+cDC1s were strongly associated with clinical outcomes across multiple types of cancer Hansen et al. (2017)
DCs are active players that indirectly inhibit melanoma cell proliferation (Tucci et al. 2019)
Under anti-tumor immune pressure, various cancer cells can develop DCs to boost immune tolerance (Wculek et al. 2020)
Immune-stimulating DCs can activate strong antitumor responses during cancer immunoediting's removal and balance phases (Wu and Horuzsko 2009)
The presence of biofilms is supposed to be associated with an increase in the number of DCs responsible for presenting antigens in chronic rhinosinusitis with nasal polyposis (Karosi et al. 2013)
Polymicrobial synergy in oral biofilm invades dendritic cells (El-Awady et al. 2019)
Functional roles of viral biofilms include: viral transmission, escape from plasmacytoid (pDC) assays (Maali et al. 2020)
MDSC (myeloid-derived suppressor cell) MDSCs are the most observed neutrophil-like cell community of cancer development, present in large numbers in many cancer models (Injarabian et al. 2019)
MDSCs suppress antitumor immunity and promote other facets of tumor development, such as tumor angiogenesis, tumor cell attack, and the creation of pre-metastatic niches (Gao et al. 2020; Condamine et al. 2015)
MDSCs are directly involved in the negative impact of patient responses to cancer therapies, including immune therapies (Diaz-Montero et al. 2009; Tada et al. 2016)
The current view is that monocyte MDSCs (M-MDSCs) and PMN-MDSCs differentiate in the same monocyte and neutrophil pathways. Their spread in cancer increases with increasing GM-CSF production, CSF-1, and other growth factors (Ostrand-Rosenberg and Bronte 2012)
MDSCs play an essential role in strengthening the tumor and a state of immunological anergy and tolerance
Functional features MDSCs in cancer are formed by factors produced by the tumor and natural host cells (Tcyganov et al. 2018)
MDSCs are significantly increased in both models of cancer mice and patients with head and neck, breast, non-small cell lungs, and kidney (Bronte et al. 2001; Nagaraj and Gabrilovich 2008; Sinha et al. 2007)
Biofilm-associated MDSCs are of a granulocyte race based on their transcriptomic profile similar to PMNs and can be classified as granulocyte MDSCs (G-MDSCs) (Heim et al. 2018)
MDSCs have played an essential role in enhancing the biofilm persistence of S. aureus, which affects both bacterial and host-derived products (Heim et al. 2014, 2015; Scherr et al. 2014)
It is not clear whether the predominance of MDSCs in biofilms is due to their active uptake by chemokines or whether these cells proliferate at the site of infection (Heim et al. 2018)
In the mouse model of S. aureus orthopedic implant infection, MDSCs represent primary infiltration and play a key role in transforming the local environment into an anti-inflammatory environment like biofilm durability (Heim et al. 2014, 2015, 2015)
The production of IL-10 by MDSCs is a mechanism used to enhance biofilms' persistence (Heim et al. 2015)
Increased MDSC can be a mechanism to control the initial inflammatory response to bacteria and inadvertently pave the way to form biofilms and remain on these devices for a long time (Heim et al. 2018)
S. aureus biofilms preferably employ MDSCs, which enhance the anti-inflammatory properties of monocytes and macrophages (2018)
Decreasing MDSC improves clearance by enhancing monocyte proinflammatory activity (Heim et al. 2014, 2015)