T Cells and Adoptive Immunotherapy: Recent Developments and Future Prospects in Gastrointestinal Oncology

Gastrointestinal oncology is one of the foremost causes of death: the gastric cancer accounts for 10.4% of cancer deaths worldwide, the pancreatic cancer for 6%, and finally, the colorectal cancer for 9% of all cancer-related deaths. For all these gastrointestinal cancers, surgical tumor resection remains the primary curative treatment, but the overall 5-year survival rate remains poor, ranging between 20–25%; the addition of combined modality strategies (pre- or postoperative chemoradiotherapy or perioperative chemotherapy) results in 5-year survival rates of only 30–35%. Therefore, many investigators believe that the potential for making significant progress lies on understanding and exploiting the molecular biology of gastrointestinal tumors to investigate new therapeutic strategies such as specific immunotherapy. In this paper we will focus on recent knowledge concerning the role of T cells and the use of T adoptive immunotherapy in the treatment of gastrointestinal cancers.

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The Role of Co-Signaling Molecules in Psoriasis and Their Implications for Targeted Treatment

Frontiers in Pharmacology ◽

10.3389/fphar.2021.717042 ◽

2021 ◽

Vol 12 ◽

Author(s):

Suqing Liu ◽

Jinhua Xu ◽

Jinfeng Wu

Keyword(s):

T Cells ◽

Signaling Molecules ◽

Pathological Process ◽

T Cell Response ◽

Significant Progress ◽

Broad Application ◽

Immune Mediated ◽

Inhibitory Molecules ◽

Application Prospects

Psoriasis is a chronic, systemic immune-mediated inflammatory disease manifesting in the skin, joint or both. Co-signaling molecules are essential for determining the magnitude of the T cell response to the antigen. According to the function of co-signaling molecules, they can be divided into co-stimulatory molecules and co-inhibitory molecules. The role of co-signaling molecules in psoriasis is recognized, mainly including the co-stimulatory molecules CD28, CD40, OX40, CD27, DR3, LFA-1, and LFA-3 and the co-inhibitory molecules CTLA-4, PD-1, and TIM-3. They impact the pathological process of psoriasis by modulating the immune strength of T cells, regulating the production of cytokines or the differentiation of Tregs. In recent years, immunotherapies targeting co-signaling molecules have made significant progress and shown broad application prospects in psoriasis. This review aims to outline the possible role of co-signaling molecules in the pathogenesis of psoriasis and their potential application for the treatment of psoriasis.

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Protective Role of Gamma Interferon during the Recall Response to Influenza Virus

Journal of Virology ◽

10.1128/jvi.72.8.6637-6645.1998 ◽

1998 ◽

Vol 72 (8) ◽

pp. 6637-6645 ◽

Cited By ~ 85

Author(s):

Adrian Bot ◽

Simona Bot ◽

Constantin A. Bona

Keyword(s):

T Cells ◽

Influenza Virus ◽

Survival Rates ◽

Protective Role ◽

Gamma Interferon ◽

H3n2 Virus ◽

Wild Type ◽

Ifn Γ ◽

Local Recruitment

ABSTRACT During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-γ). We assessed the contribution of IFN-γ to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-γ−/− mice previously immunized with the A/HK/68 (H3N2) virus. The IFN-γ−/− mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the A/WSN/33 virus. This was associated with an impaired ability of the IFN-γ−/− mice to completely clear the pulmonary virus by day 7 after the challenge, although significant reduction of the virus titers was noted. However, the IFN-γ−/− mice developed type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution assay for the estimation of CTL precursor frequency. The pulmonary recruitment of T cells in IFN-γ−/− mice was not dramatically affected, and the percentage of CD4+ and CD8+ T cells was similar to that of wild-type mice. The T cells from IFN-γ−/− mice did not display a significant switch toward a Th2 profile. Furthermore, the IFN-γ−/− mice retained the ability to mount significant titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies. Together, these results are consistent with a protective role of IFN-γ during the heterologous response against influenza virus independently of the generation and local recruitment of cross-reactive CTLs.

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Current Understanding of the Role of PPARγin Gastrointestinal Cancers

PPAR Research ◽

10.1155/2009/816957 ◽

2009 ◽

Vol 2009 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Bing Zou ◽

Liang Qiao ◽

Benjamin C. Y. Wong

Keyword(s):

Antitumor Effect ◽

Cell Cycle Control ◽

Control Cell ◽

Multiple Roles ◽

Gastrointestinal Cancers ◽

Recent Developments ◽

Positive Results ◽

Prevention And Therapy

Numerous studies have indicated that PPARγplays multiple roles such as in inflammation, cell cycle control, cell proliferation, apoptosis, and carcinogenesis, thus PPARγcontributes to the homeostasis. Many in vitro studies have showed that ligand-induced activation of PPARγpossess antitumor effect in many cancers including CRC. However, the role of PPARγin gastrointestinal cancers, especially in colorectal cancer, is rather controversial. Nevertheless, some recent studies with the positive results on the possible application of PPARγligands, such as Bezafibrate or Rosiglitazone in gastrointestinal cancers, have suggested a potential usefulness of PPARγagonists in cancer prevention and therapy. In this review, the authors discuss the recent developments in the role of PPARγin gastrointestinal cancers.

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miRNA deregulation in childhood acute lymphoblastic leukemia: a systematic review

Epigenomics ◽

10.2217/epi-2019-0154 ◽

2020 ◽

Vol 12 (1) ◽

pp. 69-80

Author(s):

Angela Gutierrez-Camino ◽

Susana Garcia-Obregon ◽

Elixabet Lopez-Lopez ◽

Itziar Astigarraga ◽

Africa Garcia-Orad

Keyword(s):

Systematic Review ◽

Acute Lymphoblastic Leukemia ◽

Risk Stratification ◽

Genetic Markers ◽

Causes Of Death ◽

Lymphoblastic Leukemia ◽

Survival Rates ◽

Childhood Acute Lymphoblastic Leukemia ◽

Mirna Deregulation

Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent causes of death by disease in children. Accurate patient risk stratification based on genetic markers could increases survival rates. miRNAs can represent novel candidates with diagnostic, predictive and prognostic potential; however, many groups investigated their involvement with contradictory results. Aim: To clarify the role of miRNAs as biomarkers through a systematic review. Results: From a revision of 45 manuscripts, we found that miR-128 and miR-181 overexpression could represent markers for ALL diagnosis and underexpression of miR-708 and miR-99a could be markers for bad prognosis. Conclusion: These signatures could refine classification and risk stratification of patients and improve ALL outcome.

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Increased regulatory B cells are involved in immune evasion in patients with gastric cancer

Scientific Reports ◽

10.1038/s41598-019-49581-4 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Yuki Murakami ◽

Hiroaki Saito ◽

Shota Shimizu ◽

Yusuke Kono ◽

Yuji Shishido ◽

...

Keyword(s):

Gastric Cancer ◽

T Cells ◽

B Cells ◽

Immune Evasion ◽

Survival Rates ◽

Prognostic Indicator ◽

Interleukin 10 ◽

Regulatory B Cells ◽

Carboxyfluorescein Succinimidyl Ester

Abstract Accumulating evidence has indicated that immune regulatory cells are involved in the establishment of tumoral immune evasion. However, the role of regulatory B cells (Bregs) in this remains unclear. Here, we identified a role for Bregs in immune evasion in gastric cancer (GC) patients. The frequency of peripheral Bregs was significantly higher in GC patients than in healthy controls (P = 0.0023). Moreover, the frequency of CD19+CD24hiCD27+ B cells in GC tissue was significantly higher than in peripheral blood and healthy gastric tissue. Carboxyfluorescein succinimidyl ester labeling revealed that CD19+CD24hiCD27+ B cells could suppress the proliferation of autologous CD4+ T cells. Moreover, CD19+CD24hiCD27+ B cells inhibited the production of interferon-gamma by CD4+ T cells. Double staining immunohistochemistry of interleukin-10 and CD19 revealed 5-year overall survival rates of 65.4% and 13.3% in BregLow and BregHigh groups, respectively (P < 0.0001). Multivariate analysis indicated that the frequency of Bregs was an independent prognostic indicator in GC patients. Taken together, our results show the existence of Bregs in GC tissue, and indicate that they are significantly correlated with the prognosis of GC patients.

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Adoptive immunotherapy of a BALB/c lymphoma by syngeneic anti-DBA/2 immune lymphoid cells: Characterization of the effector population and evidence for the role of the host's non-T cells

Cancer Immunology Immunotherapy ◽

10.1007/bf00205576 ◽

1985 ◽

Vol 20 (3) ◽

Cited By ~ 7

Author(s):

MarioP. Colombo ◽

Mariella Parenza ◽

Giorgio Parmiani

Keyword(s):

T Cells ◽

Adoptive Immunotherapy ◽

Lymphoid Cells ◽

Effector Population

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The Role of Vaccination and Screening in Limiting the Worldwide Disease Burden of Preventable Female Cancers: A Review

Women ◽

10.3390/women1010002 ◽

2020 ◽

Vol 1 (1) ◽

pp. 16-28 ◽

Cited By ~ 1

Author(s):

Claudio Costantino ◽

Davide Alba ◽

Livia Cimino ◽

Arianna Conforto ◽

Walter Mazzucco

Keyword(s):

Breast Cancer ◽

Disease Burden ◽

Malignant Disease ◽

Causes Of Death ◽

Breast Cancer Incidence ◽

Survival Rates ◽

Incidence And Mortality ◽

Common Causes ◽

Future Burden

Cancer represents one of the most common causes of death worldwide. Among women, breast cancer is the most diagnosed cancer and the principal cause of death due to malignant disease, while cervical cancer ranks fourth for both incidence and mortality. The present review aims to analyze the epidemiology of cervical and breast cancer (incidence, mortality, survival rates, and trends). Moreover, the most important primary and secondary preventive strategies (reduction of risk factors, exposure, vaccination, cancer screening) intended to reduce the future burden of cervical and breast cancer, that should be adopted actively and free of charge, were discussed in accordance to more recent and evidence-based findings.

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Recent Advances in Oligonucleotide Therapeutics in Oncology

International Journal of Molecular Sciences ◽

10.3390/ijms22073295 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3295

Author(s):

Haoyu Xiong ◽

Rakesh N. Veedu ◽

Sarah D. Diermeier

Keyword(s):

Clinical Trials ◽

Antisense Oligonucleotides ◽

Causes Of Death ◽

Survival Rates ◽

Cancer Recurrence ◽

Small Interfering Rnas ◽

The Past ◽

Oncology Review ◽

Recent Developments ◽

Review Current

Cancer is one of the leading causes of death worldwide. Conventional therapies, including surgery, radiation, and chemotherapy have achieved increased survival rates for many types of cancer over the past decades. However, cancer recurrence and/or metastasis to distant organs remain major challenges, resulting in a large, unmet clinical need. Oligonucleotide therapeutics, which include antisense oligonucleotides, small interfering RNAs, and aptamers, show promising clinical outcomes for disease indications such as Duchenne muscular dystrophy, familial amyloid neuropathies, and macular degeneration. While no approved oligonucleotide drug currently exists for any type of cancer, results obtained in preclinical studies and clinical trials are encouraging. Here, we provide an overview of recent developments in the field of oligonucleotide therapeutics in oncology, review current clinical trials, and discuss associated challenges.

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How do histone modifications contribute to transgenerational epigenetic inheritance in C. elegans?

Biochemical Society Transactions ◽

10.1042/bst20190944 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1019-1034 ◽

Cited By ~ 1

Author(s):

Rachel M. Woodhouse ◽

Alyson Ashe

Keyword(s):

Histone Modifications ◽

Molecular Mechanisms ◽

Epigenetic Inheritance ◽

Nematode Caenorhabditis Elegans ◽

Histone Methyltransferases ◽

Transgenerational Epigenetic Inheritance ◽

C Elegans ◽

Recent Developments ◽

Gene Regulatory

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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