T CELLS ACTIVATED IN VITRO AS IMMUNOTHERAPY FOR RENAL CELL CARCINOMA: CHARACTERIZATION OF 2 EFFECTOR T-CELL POPULATIONS

2001 ◽  
pp. 299-303 ◽  
Author(s):  
NINA K. GARLIE ◽  
RUTH E. SIEBENLIST ◽  
ANN V. LEFEVER
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Populations ◽  
Effector T Cell

T-Cell Activation by Bispecific Monoclonal Antibodies for Lysis of Renal Cell Carcinoma In Vitro

1992 ◽  
pp. 156-161
Author(s):  
J. van Dijk ◽  
S. Th. Zegveld ◽  
J. D. H. van Eendenburg ◽  
E. Braakman ◽  
G. J. Fleuren ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
Cell Carcinoma ◽  
T Cell Activation ◽  
Renal Cell ◽  
Cell Activation

scholarly journals NCMP-16. IMMUNO-ONCOTHERAPY (IO) PROVOKED ENCEPHALITIS AND METASTATIC MIMICRY: PATIENT WITH HISTORY OF RENAL CELL CARCINOMA ON IO PRESENTS WITH SEIZURE, FIELD CUT, AND BRAIN MASS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi182-vi182 ◽  
Author(s):  
Na Tosha Gatson ◽  
Mayur Patel ◽  
Michelle Grant ◽  
Julie Woods ◽  
Gino Mongelluzzo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Brain Mri ◽  
Cell Populations ◽  
Fuhrman Grade ◽  
Brain Mass ◽  
Immune Mediated ◽  
History Of

Abstract With the success of immuno-oncotherapy (IO) to treat systemic cancers came the risk for multi-organ autoimmune inflammation (esophagitis, colitis, hypophysitis, pneumonitis, etc.). Immune-mediated encephalitis, however, has been only rarely described in patients treated on IO. Here we present the first case of a 70-year-old male with history of clear cell renal cell carcinoma (CCRCC, Fuhrman grade 4, April 2017) post-nephrectomy with early progressive pulmonary metastases treated with pazopanib before switching to single-agent nivolumab (February 2018) with demonstrated early response. Further progression (March 2019) added body irradiation and continued systemic nivolumab with questionable medication-induced dermatitis. Patient presented to ED in May 2019 with new-onset generalized tonic-clonic seizure, left visual field cut, and 4.6cm heterogeneous enhancing right occipital mass with vasogenic edema on brain MRI, presumed metastasis. However, unknown to the patient was a remote area of right occipital encephalomalacia (found on skull-based portion of staging PET, July 2018) presumed silent stroke or TBI endorsed 20-years-ago. Patient started anti-epileptic therapy and underwent negative CSF evaluation before neurosurgical resection. Tissue pathology concerning for lymphoproliferative malignancy versus reactive lymphocytic infiltrate with perivascular distribution of monomorphic CD4+ T-cell predominance (97%) and positive T-cell receptor (gamma, beta) gene rearrangement. While clonal T-cell populations are highly suggestive of T-cell malignancies, reactive conditions can also rarely show clonal T-cell populations. Patient underwent a negative systemic staging for lymphoma and IO was discontinued without immediate initiation of steroids. Follow up clinical evaluation reveal patient improved off IO therapy. Patient was determined to have reactive immune-mediated encephalitis secondary to IO therapy causing seizure mimicking brain metastasis of primary CCRCC. Interestingly, the prior area of encephalomalacia allowed for a cellular bed to collect, resembling brain mass. Upfront staging brain MRI prior to starting IO might have revealed susceptible area and could be considered in these patients

Characterization of a Renal Cell Carcinoma Cell Line Suitable as a Target for Immunological Studies in Vitro and in the NU/NU Mouse

1985 ◽  
Vol 134 (6) ◽  
pp. 1271-1275 ◽  
Author(s):  
Martin H. Goldrosen ◽  
Robert Huben ◽  
Glenn A. Miller ◽  
David A. Lewis ◽  
Hisako Ochi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Renal Cell ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line ◽  
Renal Cell Carcinoma Cell

Metabolic barriers to immunotherapy in renal cell carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11560-11560
Author(s):  
Katy Beckermann ◽  
Peter Siska ◽  
Frank Mason ◽  
Kimryn Rathmell ◽  
Jeffrey C Rathmell
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Mitochondrial Morphology ◽  
Dependent Manner ◽  
Syngeneic Mouse Model ◽  
Healthy Control

11560 Background: Cancer cells can inhibit effector T cells through both immunomodulatory receptors and alteration of the tumor microenvironment as a result of cancer metabolism. A majority of patients treated with immune checkpoint inhibitors recently approved by the FDA fail to exhibit a clinical response. The extent to which metabolic conditions within the tumor impede T cell activation and anti-tumor effector function in renal cell carcinoma (RCC) are unknown. Methods: Under the IACUC protocol M1600005-00, BALB/c or Rag mice were subcutaneously injected with 100,000 Renca cells obtained from ATCC and growth monitored by caliper measurements in 3 dimensions every 3 days. In vivoPD-1 blockade was performed by 200 mcg/i.p. injection every 3 days using purified mPD-1 (BioXcell, J43). Deidentified tissue donations from patients with RCC were collected under the IRB protocol #151549 and processed into single cell suspensions following mechanical dissociation for the functional assays indicated below. Results: Through work with Rag deficient mice lacking functional B and T cells, we have established that tumor growth is regulated in a T cell dependent manner as evidenced by earlier formation and faster tumor growth. In a syngeneic mouse model of RCC (RenCa), we find that inhibition of PD-1 delays tumor growth and size. Tumor infiltrating lymphocytes (TILs) were abundant in patient-derived RCC, but are phenotypically distinct and are impaired both functionally and metabolically from healthy control. Instead of efficient use of aerobic glycolysis, TILs fail to increase glucose metabolism, and instead display increased reactive oxygen species (ROS) and mitochondrial dysfunction. CD8 effector cells found in tumors have notable differences in mitochondrial morphology compared to healthy control CD8 T cells by electron microscopy and immunofluorescence where CD8 TIL are punctate and dispersed throughout the cell while healthy control CD8 mitochondria are fused in networks. Thus bypassing metabolic defects may partially restore TIL activation. Conclusions: Preclinical data suggests that improved understanding of metabolic dysfunction in TILs of RCC may allow for combined therapies to improve response rates of checkpoint inhibition in this disease.

TREATMENT OF RENAL CELL CARCINOMA WITH AUTOLYMPHOCYTE THERAPY USING IN VITRO ACTIVATED T-CELLS

1992 ◽  
Vol 11 (2) ◽  
pp. 120
Author(s):  
Bruce Babbitt ◽  
Esteban Celis ◽  
Susan Ross ◽  
Amy Bolwerk ◽  
Jane Clark ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Activated T Cells

scholarly journals JAK3/STAT5/6 Pathway Alterations Are Associated with Immune Deviation inCD8+T Cells in Renal Cell Carcinoma Patients

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Elisabetta Cavalcanti ◽  
Margherita Gigante ◽  
Vito Mancini ◽  
Michele Battaglia ◽  
Pasquale Ditonno ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Cycle Regulation ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Cycle Regulation

To investigate the molecular mechanisms underlying altered T cell response in renal cell carcinoma (RCC) patients, we compared autologous and allogeneicCD8+T cell responses against RCC line from RCC patients and their HLA-matched donors, using mixed lymphocyte/tumor cell cultures (MLTCs). In addition, we analyzed the expression of molecules associated with cell cycle regulation. Autologous MLTC responderCD8+T cells showed cytotoxic activity against RCC cell lines; however the analysis of the distribution ofCD8+T-cell subsets revealed that allogenic counterparts mediate superior antitumor efficacy. In RCC patients, a decreased proliferative response to tumor, associated with defects in JAK3/STAT5/6 expression that led to increased p27KIP1 expression and alterations in the cell cycle, was observed. These data define a molecular pathway involved in cell cycle regulation that is associated with the dysfunction of tumor-specificCD8+effector cells. If validated, this may define a therapeutic target in the setting of patients with RCC.

scholarly journals Elevated Levels of Select Gangliosides in T Cells from Renal Cell Carcinoma Patients Is Associated with T Cell Dysfunction

2009 ◽  
Vol 183 (8) ◽  
pp. 5050-5058 ◽  
Author(s):  
Soumika Biswas ◽  
Kaushik Biswas ◽  
Amy Richmond ◽  
Jennifer Ko ◽  
Sankar Ghosh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cell Dysfunction ◽  
T Cell Dysfunction

scholarly journals Intratumoral CXCL13+CD8+T cell infiltration determines poor clinical outcomes and immunoevasive contexture in patients with clear cell renal cell carcinoma

2021 ◽  
Vol 9 (2) ◽  
pp. e001823
Author(s):  
Siyuan Dai ◽  
Han Zeng ◽  
Zhaopei Liu ◽  
Kaifeng Jin ◽  
Wenbin Jiang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Immune Function ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Tnf Α ◽  
Ifn Γ

BackgroundChemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4+T cells (TFH) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by TFH have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8+T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13+CD8+T cells in clear cell renal cell carcinoma (ccRCC).MethodsWe analyzed prognostic value and immune contexture that associated with CXCL13+CD8+T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13+CD8+T cells and total CD8+T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC.ResultsIntratumoral CXCL13+CD8+T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13+CD8+T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8+T cells in high-level CXCL13+CD8+T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13+CD8+T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3+ regulatory T cells, TLS and decreased natural killer cells, GZMB+ cells.ConclusionsIntratumoral CXCL13+CD8+T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13+CD8+T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13+CD8+T cells abundance impaired total CD8+T cells’ immune function. Intratumoral CXCL13+CD8+T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13+CD8+T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.

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