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Tumor Immunology & Immunotherapy
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Tumor Immunology & Immunotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 31828

Special Issue Editor

Prof. Dr. Sherven Sharma

E-Mail Website
Guest Editor
Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Interests: therapeutic cancer vaccines; tumor immunology; immune suppression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor induced immune suppression and tolerance mediated by T regulatory cells, myeloid derived suppreesor cells (MDSC), tumor associated macrophages (TAMs) suppressive dendritic cells, TLRs and IL-10, TGFb and IL-8 in the tumor microenvironment inhibit active immune responses  promoting  tumor growth. These inhibitory molecular and cellular pathways have highlighted the need to find approaches disabling these dysfuntional immune suppressive mechanisms for precision immune therapy against cancer. We invite you to submit research articles, reviews and short communications on this topic of intense investigation.

Prof. Dr. Sherven Sharma
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • Tumor Immunology
  • T regulatory cells
  • Immune suppresion
  • MDSCs
  • TAMs
  • TGF
  • IL-10
  • IL-8
  • TLRs

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Published Papers (6 papers)

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Research

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14 pages, 2521 KiB  
Article
TGF-β/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma
by Kyung-Eun Noh, Jun-Ho Lee, So-Yeon Choi, Nam-Chul Jung, Ji-Hee Nam, Ji-Soo Oh, Jie-Young Song, Han Geuk Seo, Yu Wang, Hyun Soo Lee and Dae-Seog Lim
Int. J. Mol. Sci. 2021, 22(16), 8706; https://doi.org/10.3390/ijms22168706 - 13 Aug 2021
Cited by 26 | Viewed by 3676
Abstract
Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) [...] Read more.
Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) CAR (CD19 CAR) and a TGF-β/IL-7 chimeric switch receptor (tTRII-I7R) in T cells (CD19 CAR-tTRII-I7R-T cells). The tTRII-I7R was designed to convert immunosuppressive TGF-β signaling into immune-activating IL-7 signaling. The effect of TGF-β on CD19 CAR-tTRII-I7R-T cells was assessed by western blotting. Target-specific killing by CD19 CAR-tTRII-I7R-T cells was evaluated by Eu-TDA assay. Daudi tumor-bearing NSG (NOD/SCID/IL2Rγ-/-) mice were treated with CD19 CAR-tTRII-I7R-T cells to analyze the in vivo anti-tumor effect. In vitro, CD19 CAR-tTRII-I7R-T cells had a lower level of phosphorylated SMAD2 and a higher level of target-specific cytotoxicity than controls in the presence of rhTGF-β1. In the animal model, the overall survival and recurrence-free survival of mice that received CD19 CAR-tTRII-I7R-T cells were significantly longer than in control mice. These findings strongly suggest that CD19 CAR-tTRII-I7R-T cell therapy provides a new strategy for long-lasting, TGF-β-resistant anti-tumor effects against B cell lymphoma, which may lead ultimately to increased clinical efficacy. Full article
(This article belongs to the Special Issue Tumor Immunology & Immunotherapy)
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Review

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13 pages, 282 KiB  
Review
Immunomodulatory Arming Factors—The Current Paradigm for Oncolytic Vectors Relies on Immune Stimulating Molecules
by Cole W. D. Peters and Fares Nigim
Int. J. Mol. Sci. 2021, 22(16), 9051; https://doi.org/10.3390/ijms22169051 - 22 Aug 2021
Cited by 2 | Viewed by 2002
Abstract
The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes [...] Read more.
The dogma of engineering oncolytic viral vectors has shifted from emphasizing the viral lysis of individual cancer cells to the recruitment and coordination of the adaptive immune system to clear the tumor. To accomplish this, researchers have been adding several classes of transgenes to their preferred viral platforms. The most prevalent of these include antibodies and targeting moieties, interleukins and cytokines, and genes which rely on small molecule co-administration for tumor killing. Most current vectors rely exclusively on one of these types of transgenes to elicit the desired immune response to clear tumors, but are not mutually exclusive, with several larger OVs armed with several of these factors. The common theme of emerging armed vectors is to simply initiate or enhance infiltration of effector CD8+ T cells to clear the tumor locally at OV infection sites, and systemically throughout the body where the OV has not infected tumor cells. The precision of oncolytic vectors to target a cell type or tissue remains its key advantage over small-molecule drugs. Unlike chemo- and other drug therapies, viral vectors can be made to specifically infect and grow within tumor cells. This ensures localized expression of the therapeutic transgene to the diseased tissue, thereby limiting systemic toxicity. This review will examine the immunomodulating transgenes of current OVs, describe their general effect on the immune system, and provide the rationale for each vector’s use in clearing its targeted tumor. Full article
(This article belongs to the Special Issue Tumor Immunology & Immunotherapy)
13 pages, 1200 KiB  
Review
CD39 Regulation and Functions in T Cells
by Eleonora Timperi and Vincenzo Barnaba
Int. J. Mol. Sci. 2021, 22(15), 8068; https://doi.org/10.3390/ijms22158068 - 28 Jul 2021
Cited by 80 | Viewed by 8498
Abstract
CD39 is an enzyme which is responsible, together with CD73, for a cascade converting adenosine triphosphate into adenosine diphosphate and cyclic adenosine monophosphate, ultimately leading to the release of an immunosuppressive form of adenosine in the tumor microenvironment. Here, we first review the [...] Read more.
CD39 is an enzyme which is responsible, together with CD73, for a cascade converting adenosine triphosphate into adenosine diphosphate and cyclic adenosine monophosphate, ultimately leading to the release of an immunosuppressive form of adenosine in the tumor microenvironment. Here, we first review the environmental and genetic factors shaping CD39 expression. Second, we report CD39 functions in the T cell compartment, highlighting its role in regulatory T cells, conventional CD4+ T cells and CD8+ T cells. Finally, we compile a list of studies, from preclinical models to clinical trials, which have made essential contributions to the discovery of novel combinatorial approaches in the treatment of cancer. Full article
(This article belongs to the Special Issue Tumor Immunology & Immunotherapy)
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19 pages, 8906 KiB  
Review
The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression
by Huogang Wang, Mingo M. H. Yung, Hextan Y. S. Ngan, Karen K. L. Chan and David W. Chan
Int. J. Mol. Sci. 2021, 22(12), 6560; https://doi.org/10.3390/ijms22126560 - 18 Jun 2021
Cited by 130 | Viewed by 8890
Abstract
Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget’s “Seed [...] Read more.
Rather than primary solid tumors, metastasis is one of the hallmarks of most cancer deaths. Metastasis is a multistage event in which cancer cells escape from the primary tumor survive in the circulation and disseminate to distant sites. According to Stephen Paget’s “Seed and Soil” hypothesis, metastatic capacity is determined not only by the internal oncogenic driving force but also by the external environment of tumor cells. Throughout the body, macrophages are required for maintaining tissue homeostasis, even in the tumor milieu. To fulfill these multiple functions, macrophages are polarized from the inflammation status (M1-like) to anti-inflammation status (M2-like) to maintain the balance between inflammation and regeneration. However, tumor cell-enforced tumor-associated macrophages (TAMs) (a high M2/M1 ratio status) are associated with poor prognosis for most solid tumors, such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up to 50% of the tumor mass, exert both protumor and immunosuppressive effects in promoting tumor metastasis through secretion of interleukin 10 (IL10), transforming growth factor β (TGFβ), and VEGF, expression of PD-1 and consumption of arginine to inhibit T cell anti-tumor function. However, the underlying molecular mechanisms by which the tumor microenvironment favors reprogramming of macrophages to TAMs to establish a premetastatic niche remain controversial. In this review, we examine the latest investigations of TAMs during tumor development, the microenvironmental factors involved in macrophage polarization, and the mechanisms of TAM-mediated tumor metastasis. We hope to dissect the critical roles of TAMs in tumor metastasis, and the potential applications of TAM-targeted therapeutic strategies in cancer treatment are discussed. Full article
(This article belongs to the Special Issue Tumor Immunology & Immunotherapy)
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11 pages, 648 KiB  
Review
Functional Ambivalence of Dendritic Cells: Tolerogenicity and Immunogenicity
by Ji-Hee Nam, Jun-Ho Lee, So-Yeon Choi, Nam-Chul Jung, Jie-Young Song, Han-Geuk Seo and Dae-Seog Lim
Int. J. Mol. Sci. 2021, 22(9), 4430; https://doi.org/10.3390/ijms22094430 - 23 Apr 2021
Cited by 20 | Viewed by 3527
Abstract
Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the [...] Read more.
Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the method of induction and/or the presence of immunosuppressive agents. Tolerogenic dendritic cells (tDCs) induce immune tolerance by activating CD4+CD25+Foxp3+ regulatory T (Treg) cells and/or by producing cytokines that inhibit T cell activation. These findings suggest that tDCs may be an effective treatment for autoimmune diseases, inflammatory diseases, and infertility. Full article
(This article belongs to the Special Issue Tumor Immunology & Immunotherapy)
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20 pages, 664 KiB  
Review
The Emerging Clinical Role of Spermine in Prostate Cancer
by Qiang Peng, Christine Yim-Ping Wong, Isabella Wai-yin Cheuk, Jeremy Yuen-Chun Teoh, Peter Ka-Fung Chiu and Chi-Fai Ng
Int. J. Mol. Sci. 2021, 22(9), 4382; https://doi.org/10.3390/ijms22094382 - 22 Apr 2021
Cited by 15 | Viewed by 3930
Abstract
Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction [...] Read more.
Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management. Full article
(This article belongs to the Special Issue Tumor Immunology & Immunotherapy)
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