Potential Role of Tumor Cell Antigen Modulation in Cancer Immunotherapy

The peptidylarginine deiminases (PADs) are a family of posttranslational modification enzymes that catalyze the conversion of positively charged protein-bound arginine and methylarginine residues to the uncharged, nonstandard amino acid citrulline. This enzymatic activity is referred to as citrullination or, alternatively, deimination. Citrullination can significantly affect biochemical pathways by altering the structure and function of target proteins. Five mammalian PAD family members (PADs 1–4 and 6) have been described and show tissue-specific distribution. Recent reviews on PADs have focused on their role in autoimmune diseases. Here, we will discuss the potential role of PADs in tumor progression and tumor-associated inflammation. In the context of cancer, increasing clinical evidence suggests that PAD4 (and possibly PAD2) has important roles in tumor progression. The link between PADs and cancer is strengthened by recent findings showing that treatment of cell lines and mice with PAD inhibitors significantly suppresses tumor growth and, interestingly, inflammatory symptoms. At the molecular level, transcription factors, coregulators, and histones are functional targets for citrullination by PADs, and citrullination of these targets can affect gene expression in multiple tumor cell lines. Next generation isozyme-specific PAD inhibitors may have therapeutic potential to regulate both the inflammatory tumor microenvironment and tumor cell growth.

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Involvement of Plateletâ€“Tumor Cell Interaction in Immune Evasion. Potential Role of Podocalyxin-Like Protein 1

Frontiers in Oncology ◽

10.3389/fonc.2014.00245 ◽

2014 ◽

Vol 4 ◽

Cited By ~ 24

Author(s):

Laura Amo ◽

EstÃbaliz Tamayo-Orbegozo ◽

Natalia Maruri ◽

Cristina Eguizabal ◽

Olatz Zenarruzabeitia ◽

...

Keyword(s):

Tumor Cell ◽

Immune Evasion ◽

Potential Role ◽

Cell Interaction

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Tumor-Cell–Macrophage Fusion Cells as Liquid Biomarkers and Tumor Enhancers in Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms21051872 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1872 ◽

Cited By ~ 3

Author(s):

Yariswamy Manjunath ◽

David Porciani ◽

Jonathan B. Mitchem ◽

Kanve N. Suvilesh ◽

Diego M. Avella ◽

...

Keyword(s):

Tumor Cell ◽

Tumor Cells ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Potential Role ◽

Potential Impact ◽

Definition Of ◽

Intercellular Connections ◽

Cell Fusions

Although molecular mechanisms driving tumor progression have been extensively studied, the biological nature of the various populations of circulating tumor cells (CTCs) within the blood is still not well understood. Tumor cell fusion with immune cells is a longstanding hypothesis that has caught more attention in recent times. Specifically, fusion of tumor cells with macrophages might lead to the development of metastasis by acquiring features such as genetic and epigenetic heterogeneity, chemotherapeutic resistance, and immune tolerance. In addition to the traditional FDA-approved definition of a CTC (CD45-, EpCAM+, cytokeratins 8+, 18+ or 19+, with a DAPI+ nucleus), an additional circulating cell population has been identified as being potential fusions cells, characterized by distinct, large, polymorphonuclear cancer-associated cells with a dual epithelial and macrophage/myeloid phenotype. Artificial fusion of tumor cells with macrophages leads to migratory, invasive, and metastatic phenotypes. Further studies might investigate whether these have a potential impact on the immune response towards the cancer. In this review, the background, evidence, and potential relevance of tumor cell fusions with macrophages is discussed, along with the potential role of intercellular connections in their formation. Such fusion cells could be a key component in cancer metastasis, and therefore, evolve as a diagnostic and therapeutic target in cancer precision medicine.

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Potential Role of CD47-Directed Bispecific Antibodies in Cancer Immunotherapy

Frontiers in Immunology ◽

10.3389/fimmu.2021.686031 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yan Yang ◽

Zheng Yang ◽

Yun Yang

Keyword(s):

Cancer Immunotherapy ◽

Potential Role ◽

Bispecific Antibody ◽

Lymphoblastic Leukemia ◽

Bispecific Antibodies ◽

The Novel ◽

Mechanisms Of Resistance ◽

Immunological Therapy ◽

Novel Targets

The prosperity of immunological therapy for cancer has aroused enormous passion for exploiting the novel targets of cancer immunotherapy. After the approval of blinatumomab, a bispecific antibody (bsAb) targeting on CD19 for acute lymphoblastic leukemia, a few of CD47-targeted bsAbs for cancer immunotherapy, are currently in clinical research. In our review of CD47-targeted bsAbs, we described the fundamental of bsAbs. Then, we summarized the information of four undergoing phase I researches, reviewed the main toxicities relevant to CD47-targeted bsAb immunological therapy of on-target cytotoxicity to healthy cells and a remarkable antigen-sink. Finally, we described possible mechanisms of resistance to CD47-targeted bsAb therapy. More clinical researches are supposed to adequately confirm its security and efficacy in clinical practice.

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The potential role of vitamin C in empowering cancer immunotherapy

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.112553 ◽

2022 ◽

Vol 146 ◽

pp. 112553

Author(s):

Takwa Bedhiafi ◽

Varghese Philipose Inchakalody ◽

Queenie Fernandes ◽

Sarra Mestiri ◽

Nashiru Billa ◽

...

Keyword(s):

Vitamin C ◽

Cancer Immunotherapy ◽

Potential Role

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POPDC proteins and cardiac function

Biochemical Society Transactions ◽

10.1042/bst20190249 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1393-1404 ◽

Cited By ~ 4

Author(s):

Thomas Brand

Keyword(s):

Potential Role ◽

Striated Muscle ◽

Short Review ◽

Effector Proteins ◽

Muscle Disease ◽

Disease Genes ◽

Protein Protein Interaction ◽

Interaction Partners ◽

And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

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