Monoclonal antibodies anti-CD3, anti-TCRαβ and anti-CD2 act synergistically with tumor cells to stimulate lymphokine-activated killer cells and tumor-infiltrating lymphocytes to secrete interferon γ

1992 ◽  
Vol 35 (5) ◽  
pp. 335-341 ◽  
Author(s):  
Anita S. -F. Chong ◽  
Edgar D. Staren ◽  
Philip Scuderi
1995 ◽  
Vol 81 (6) ◽  
pp. 445-449 ◽  
Author(s):  
Laura Fabbri ◽  
Ruggero Ridolfi ◽  
Angela Riccobon ◽  
Roberta Maltoni ◽  
Emanuela Flamini ◽  
...  

A 37-year-old patient with liver metastases from gastric cancer was treated with a double adoptive immunotherapy regimen comprising tumor-infiltrating lymphocytes plus interleukin-2 and subsequently local-regional lymphokine-activated killer cells plus interleukin-2 because of an extremely high in vitro cytotoxic specific activity on established gastric cancer cell lines. The necrosis verified in the center of the hepatic metastasis would appear to demonstrate treatment efficacy, but no clinical response was seen. In vitro cytotoxicity data alone are insufficient to predict the clinical efficacy of adoptive immunotherapy.


2021 ◽  
Vol 160 ◽  
pp. 103261
Author(s):  
Mélanie Gauthier ◽  
Caroline Laroye ◽  
Danièle Bensoussan ◽  
Cédric Boura ◽  
Véronique Decot

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
F. Pandolfi ◽  
R. Cianci ◽  
D. Pagliari ◽  
F. Casciano ◽  
C. Bagalà ◽  
...  

Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes.


2006 ◽  
Vol 19 (1) ◽  
pp. 205873920601900 ◽  
Author(s):  
S. Staibano ◽  
M. Mascolo ◽  
F. Tranfa ◽  
G. Salvatore ◽  
C. Mignogna ◽  
...  

Experimental and clinical evidence indicate that immunological mechanisms might be important in the clinical course of uveal malignant melanoma (UMM). We analyzed the amount and phenotype of tumor infiltrating lymphocytes (TIL) and the expression of the apoptosis-inducing molecule Fas and its ligand, FasL, on tumor cells and TIL in a selected series of UMM with the aim to establish if a correlation between their expression and the clinical behavior of UMM exists. TIL phenotype and Fas/FasL expression were evaluated by immunohistochemistry in 61 cases of formalin-fixed, paraffin-embedded UMM. Results were compared with the follow-up data of patients. Most of the UMM showed a prevalence of CD8+ CD3+ T lymphocytes, or CD4+ and CD8+ cells in equal amounts. UMM showed a variable expression of FasL, ranging from 0 to > 40% of neoplastic cells. Fas was always expressed in TIL, although with a variable extent. A subgroup of UMM showed in TIL a strongly reduced or even absent expression of TCR ζ-chain, involved in activation of T-lymphocytes. This subgroup was characterized by a worse outcome. We hypothesized that an impaired cytotoxic immune response due to the loss of the ζ-chain expression plays a primary role in the biological course of UMM. Our results indicate that the overcoming of the impairment of TCR function may represent a prerequisite for the development of new therapeutic strategies for managing UMM, suggesting that elimination of tumor cells may be possible by activation of cytotoxic cells present within ocular melanomas.


2017 ◽  
Vol 1 (5) ◽  
pp. 487-492
Author(s):  
Hee Joon Bae ◽  
Shutong Liu ◽  
Ping Jin ◽  
David Stroncek

Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are a multipotent, heterogeneous population of cells that play a critical role in wound healing and tissue regeneration. MSCs, found in the tumor microenvironment, support tumor growth through the production of angiogenic factors, growth factors and extracellular matrix proteins. They also have immunomodulatory properties, and since they produce indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2) and transforming growth factor β (TGF-β), they have been thought to have primarily immunosuppressive effects. However, their role in the tumor microenvironment is complex and demonstrates plasticity depending on location, stimulatory factors and environment. The presence of melanoma-activated tumor-infiltrating lymphocytes (TILs) has been shown to produce pro-inflammatory changes with TH1 (type 1T helper)-like phenotype in MSCs via activated-TIL released cytokines such as interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin-1α (IL-1α), while simultaneously producing factors, such as IDO1, which have been traditionally associated with immunosuppression. Similarly, the combination of IFN-γ and TNF-α polarizes MSCs to a primarily TH1-like phenotype with the expression of immunosuppressive factors. Ultimately, further studies are encouraged and needed for a greater understanding of the role of MSCs in the tumor microenvironment and to improve cancer immunotherapy.


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