CC Chemokine Receptor 5: The Interface of Host Immunity and Cancer

Oliveira, Carlos Eduardo Coral de; Oda, Julie Massayo Maeda; Guembarovski, Roberta Losi; Oliveira, Karen Brajão de; Ariza, Carolina Batista; Neto, Jamil Soni; Hirata, Bruna Karina Banin; Watanabe, Maria Angelica Ehara

doi:10.1155/2014/126954

Cited by 49 publications

(37 citation statements)

References 76 publications

(89 reference statements)

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“…Remarkably, TAB also expressed numerous chemokines including T (reg) cell, and macrophage chemoattractants CCL3, CCL3L1, CCL4, CCL5, CCL28 and CXCL16 [30][31][32][33] in plasmablast-like B cells ( Figure 3C). Together, these results indicate that TIPB are able to regulate inflammation and shape the cellular composition of the human melanoma TME.…”

Section: Melanoma Conditioned Medium Induces a Plasmablast-like Dominmentioning

confidence: 99%

B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

Griss

Bauer

Wagner

et al. 2018

Preprint

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Tumor associated inflammation predicts response to immune checkpoint blockade in human melanoma. Established mechanisms that underlie therapy response and resistance center on anti-tumor T cell responses.Here we show that tumor-associated B cells are vital to tumor associated inflammation.Autologous B cells were directly induced by melanoma conditioned medium, expressed proand anti-inflammatory factors, and differentiated towards a plasmablast-like phenotype in vitro .We could identify this phenotype as a distinct cluster of B cells in an independent public single-cell RNA-seq dataset from melanoma tumors. There, plasmablast-like tumor-associated B cells showed expression of CD8+T cell-recruiting chemokines such as CCL3, CCL4, CCL5 and CCL28. Depletion of tumor associated B cells in metastatic melanoma patients by anti-CD20 immunotherapy decreased overall inflammation and CD8+T cell numbers in the human melanoma TME. Conversely, the frequency of plasmablast-like B cells in pretherapy melanoma samples predicted response and survival to immune checkpoint blockade in two independent cohorts. Tumor-associated B cells therefore orchestrate and sustain tumor inflammation, recruit CD8+ T effector cells and may represent a predictor for response and survival to immune checkpoint blockade in human melanoma.2 Cancers such as melanoma, lung, and kidney cancer often present with an inflamed but immunosuppressive tumor microenvironment (TME). Immune checkpoint blocking (ICB) antibodies have significantly improved cancer therapy by overcoming inhibition of T cell effector functions. Yet, a considerable number of patients does not benefit from ICB therapy 1 . It is therefore key to understand the mechanisms that regulate inflammation within the TME to develop novel therapies and improve patient survival. B cells promote both acute immune-associated inflammation for protection against foreign pathogens as well as chronic inflammation in autoimmune diseases and persistent infection. Mouse cancer models show that tumor-associated B cells (TAB) promote tumor inflammation 2,3 but may also inhibit anti-tumor T cell-dependent therapy responses 4-7 . The immuno-inhibitory function of TAB in these models resembles that of regulatory B cells (Breg), which are an established source of inhibitory cytokines such as IL-10 and TGF-b (reviewed in 8 ). In human cancer, Breg were described by either phenotyping, direct detection of immunoinhibitory cytokines or surface molecules, and/or immunosuppressive function 4,[9][10][11][12][13] .Often Breg frequencies increase with tumor progression and are enriched in tumors compared to peripheral blood or adjacent normal tissue. Increased IL-10 + B cell numbers can also be accompanied by increased numbers of CD4 + CD25 +/high CD127 low/and Foxp3 + Tregs in tumor tissues 10,12,14,15 which were independently associated with tumor progression or reduced patient survival.In human melanoma, up to 33% of the immune cells can be TAB 16,17 and phenotypic analysis has revealed CD20+ TAB (reviewed in 18 ) and CD1...

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“…In a similar way to T cells, NK cell subpopulations have a number of immunoregulatory functions and can kill their targets via the secretion of interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα) and T cell recruiting chemokines (RANTES, MIP1α, MIP1β), and the induction of apoptosis via Fas-Fas ligand and TRAILreceptor interactions, and the release of granzyme B and perforin [54][55][56][57][58][59][60][61]. The recognition of the Fc component of antibodies which have bound to tumor-specific or tumor-associated antigens by NK cells triggers antibody-dependent cellular cytotoxicity (ADCC), and thereby establishes a link between B cell and NK cell-mediated immune responses.…”

Section: Hsps As Targets For Adaptive and Innate Immune Responsesmentioning

confidence: 99%

The role of heat shock protein 70 (Hsp70) in radiation-induced immunomodulation

et al. 2015

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Despite enormous progress in radiation technologies (high precision image-guided irradiation, proton irradiation, heavy ion irradiation) and radiotherapeutic concepts (hypofractionated irradiation schemes), the clinical outcome of radiotherapy in locally advanced and metastasized tumors and in hypoxic tumors which are radiation-resistant remains unsatisfactory. Given their key influence on a number of biological and immunological parameters, this article considers the influence of irradiation-induced stress proteins on radiation-induced immunomodulation. Depending on its location, the major stress-inducible Heat shock protein 70 (Hsp70) has been found to fulfill multiple roles. On the one hand, increased intracellular Hsp70 levels have been found to play a key role in the recovery from stress such as radio(chemo)therapy, and on the other hand extracellular Hsp70 proteins are potent stimulators of the innate immune system and mediators of anti-tumor immunity. Furthermore, if loaded with tumor-derived peptides, members of the Heat Shock Protein 70 (HSP70) and 90 (HSP90) families can stimulate the adaptive immune system via antigen cross-presentation. An irradiation-induced enhancement of the selective expression of a membrane form of Hsp70 on the surface of tumor cells which can act as a recognition structure for activated NK cells might have significant clinical relevance, in that the outcome of irradiation therapy for advanced tumors could be improved by combining it with cell-based and other immunotherapies that target this membrane form of Hsp70.

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“…Some authors reported higher CCR5 expression in primary CRC with increased local growth [20,21], while others have found that high CCR5 expression is required for metastasis [22,23]. In addition to this, it is presumed that variations in expressional pattern of CCR5 can alter the immune response system in CRC, which in turn will favor the further progression of the disease [24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells

et al. 2015

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Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

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“…It can explain the strong correlation between cervical precancerous lesions regression rate and presence of intraepithelial cytotoxic T cells. Therefore, patients carrying the Δ32 deletion even in heterozygosis might present an immune response impairment against the virus, resulting in persistent infection, favouring cervical intraepithelial lesions development (Oliveira et al, ; Da Silva et al, ; Westrich, Warren, & Pyeon, ; Woo et al, ).…”

Section: Discussionmentioning

confidence: 99%

CCR5genetic variants and epidemiological determinants for HPV infection and cervical premalignant lesions

et al. 2019

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Human papillomavirus (HPV) infection can lead to the development of productive epithelial lesions and cervical cancer. Most cervical HPV infections are solved by cell‐mediated immunity within 1–2 years, and it is known that chronic inflammation predisposes to lesions progression and tumour development. In this context, we highlight the CC chemokine receptor 5 (CCR5) which is involved in leucocytes chemotaxis to sites of inflammation, controlling the immune response. The CCR5 rs333 genotyping of 164 HPV infected women and 185 non‐infected women was performed using polymerase chain reaction (PCR). HPV infection was more frequent among women under 34 years old (p < 0.001), single (p = 0.001), that received 1 minimum wage or less (p = 0.002), tobacco smokers (p = 0.007), who had the first sexual intercourse before 17 years old (p = 0.038) and that had 4 or more sexual partners during lifetime (p = 0.001). No significant difference regarding genotypes and alleles distribution according to HPV infection was observed. CCR5/CCR5 genotype was observed in 94.1% of HPV non‐infected women and in 89% of infected ones, CCR5/Δ32 in 5.9% of HPV infected and in 10.4% of non‐infected women, and Δ32/Δ32 was observed in only one (0.6%) infected patient. CCR5 genotypes were also not associated with cervical lesions development among HPV infected women (p = 0.167). Since CCR5 may control the antitumour immune response and cervical lesions and the studied rs333 polymorphism is not very frequent, other studies are necessary, in order to establish CCR5 role on HPV infection and squamous intraepithelial lesions development.

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“…The leukocytes include several types of cells that play a significant role in the development of pathological conditions such as diabetes and cancer [4][5][6]. The pathway PI3K/Akt is involved in the activation of macrophages and lymphocytes, secretion of cytokines, initiation of inflammatory processes and immune surveillance failure [7].…”

mentioning

confidence: 99%

Експресія протеїнкінази p70S6K у лейкоцитах хворих на рак і цукровий діабет

Vatseba¹,

Sokolova²,

Pushkarev³

et al. 2019

Endokr.

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Мета — вивчити експресію p70S6K у лейкоцитах хворих на рак і цукровий діабет. Матеріал і методи. Експресію p70S6K визначали методом імуноферментного аналізу. Результати. Показано, що в лейкоцитах хворих на рак і цукровий діабет 2-го типу кількість протеїнкінази зростає, що свідчить про посилення експресії p70S6K, яка відіграє важливу роль у формуванні інсулінорезистентності та прогресії пухлин. Проте в лейкоцитах хворих і на рак, і на цукровий діабет кількість p70S6K є істотно нижчою порівняно з такою в лейкоцитах хворих на рак або цукровий діабет. Висновки. Обговорюються можливі механізми та значення зміни експресії p70S6K у лейкоцитах.

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CC Chemokine Receptor 5: The Interface of Host Immunity and Cancer

Cited by 49 publications

References 76 publications

B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma

The role of heat shock protein 70 (Hsp70) in radiation-induced immunomodulation

CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells

CCR5genetic variants and epidemiological determinants for HPV infection and cervical premalignant lesions

Експресія протеїнкінази p70S6K у лейкоцитах хворих на рак і цукровий діабет

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