Tumor Microenvironment and Immune Effector Cells: Isolation, Large Scale Propagation and Characterization of CD8+ Tumor Infiltrating Lymphocytes From Renal Cell Carcinomas

NK cells have unique capabilities of recognition and destruction of tumor cells, without the requirement for prior immunization of the host. Maintaining tolerance to healthy cells makes them an attractive therapeutic tool for almost all types of cancer. Unfortunately, metabolic changes associated with malignant transformation and tumor progression lead to immunosuppression within the tumor microenvironment, which in turn limits the efficacy of various immunotherapies. In this review, we provide a brief description of the metabolic changes characteristic for the tumor microenvironment. Both tumor and tumor-associated cells produce and secrete factors that directly or indirectly prevent NK cell cytotoxicity. Here, we depict the molecular mechanisms responsible for the inhibition of immune effector cells by metabolic factors. Finally, we summarize the strategies to enhance NK cell function for the treatment of tumors.

Download Full-text

Immune Self-tuning in Renal Cell Carcinoma

European Oncology & Haematology ◽

10.17925/eoh.2010.06.1.70 ◽

2010 ◽

Vol 06 (01) ◽

pp. 70

Author(s):

Antonia Busse ◽

Ulrich Keilholz ◽

◽

Keyword(s):

Renal Cell Carcinoma ◽

Immune Response ◽

Cell Carcinoma ◽

Renal Cell ◽

Disease Stabilisation ◽

Tumour Regression ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Inhibitory Molecules

Although renal cell carcinoma (RCC) is an immunogenic tumour, and although there is evidence that in a small proportion of cases antitumour immune responses may mediate tumour regression or at least disease stabilisation, patients with progressive disease have no effective antitumour immune response. Besides preventing recognition of the tumour by immune effector cells, RCC escapes the immune system by induction of tolerance through manipulating the function and proliferation of immune effector cells. This tuning of the immune response can occur by active suppression of immune effector cells through inhibitory molecules expressed on the tumour surface and through various tumour-secreted soluble factors, or it can be mediated indirectly by induction of immunosuppressive cells. This review provides an overview of the most common mechanisms that mediate immune tolerance in RCC and discusses the therapeutic perspectives of immunoregulatory strategies in the era of targeted therapies.

Download Full-text

Metabolites in the Tumor Microenvironment Reprogram Functions of Immune Effector Cells Through Epigenetic Modifications

Frontiers in Immunology ◽

10.3389/fimmu.2021.641883 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yijia Li ◽

Yangzhe Wu ◽

Yi Hu

Keyword(s):

Tumor Microenvironment ◽

Cancer Cells ◽

Immune Cells ◽

Expression Patterns ◽

Immune Effector ◽

Effector Cells ◽

Cell Functions ◽

Metabolic Plasticity ◽

Signal Transduction Networks ◽

Immune Effector Cells

Cellular metabolism of both cancer and immune cells in the acidic, hypoxic, and nutrient-depleted tumor microenvironment (TME) has attracted increasing attention in recent years. Accumulating evidence has shown that cancer cells in TME could outcompete immune cells for nutrients and at the same time, producing inhibitory products that suppress immune effector cell functions. Recent progress revealed that metabolites in the TME could dysregulate gene expression patterns in the differentiation, proliferation, and activation of immune effector cells by interfering with the epigenetic programs and signal transduction networks. Nevertheless, encouraging studies indicated that metabolic plasticity and heterogeneity between cancer and immune effector cells could provide us the opportunity to discover and target the metabolic vulnerabilities of cancer cells while potentiating the anti-tumor functions of immune effector cells. In this review, we will discuss the metabolic impacts on the immune effector cells in TME and explore the therapeutic opportunities for metabolically enhanced immunotherapy.

Download Full-text

CHARACTERIZATION OF TUMOR INFILTRATING LYMPHOCYTES FROM PATIENTS WITH RENAL CELL CARCINOMA

The Japanese Journal of Urology ◽

10.5980/jpnjurol1989.87.928 ◽

1996 ◽

Vol 87 (6) ◽

pp. 928-936

Author(s):

Hitoshi Yanagiya ◽

Seiji Kudoh ◽

Shinya Takahashi ◽

Tadashi Suzuki

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Tumor Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

Download Full-text

From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

Clinical and Developmental Immunology ◽

10.1155/2011/439053 ◽

2011 ◽

Vol 2011 ◽

pp. 1-15 ◽

Cited By ~ 16

Author(s):

Oana Draghiciu ◽

Hans W. Nijman ◽

Toos Daemen

Keyword(s):

Tumor Microenvironment ◽

Current Knowledge ◽

Cancer Development ◽

Detailed Knowledge ◽

Immune Effector ◽

Effector Cells ◽

Immune Effector Cells ◽

Tumor Immunosuppression ◽

Tumor Eradication ◽

Induction Of Tolerance

Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors.

Download Full-text