Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity.

1990 ◽  
Vol 8 (10) ◽  
pp. 1618-1629 ◽  
Author(s):  
R G Steis ◽  
W J Urba ◽  
L A VanderMolen ◽  
M A Bookman ◽  
J W Smith ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ovarian Cancer ◽  
Endometrial Carcinoma ◽  
Cancer Patients ◽  
Mononuclear Cells ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Lak Cells ◽  
Small Bowel Adenocarcinoma ◽  
Colorectal Cancer Patients

Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results.

scholarly journals Association of Anger Expression-Out with NK Cell Counts in Colorectal Cancer Patients

2018 ◽  
Vol 31 (3) ◽  
pp. 152
Author(s):  
Estela Kakoo-Brioso ◽  
Luís Costa ◽  
Sílvia Ouakinin
Keyword(s):  
Colorectal Cancer ◽  
Natural Killer Cell ◽  
Cell Count ◽  
Natural Killer ◽  
Cancer Patients ◽  
Psychological Factors ◽  
Killer Cell ◽  
Anger Expression ◽  
Cell Counts ◽  
Colorectal Cancer Patients

Introduction: There is growing evidence describing the relation between psychological factors and the progression of colorectal cancer. Several mechanisms have been proposed but the one showing more promising evidence relies on the modulation of the antitumoral immune response by psychological factors, particularly through natural killer cells. We aimed to study the relation between natural killer cell count and anxiety, depression and anger state, trait and expression in 54 pre-surgical colorectal cancer patients.Material and Methods: We measured peripheral blood natural killer cell count and applied the State-Trait Anger Expression Inventory and the Hospital Anxiety and Depression Scale to 54 pre-surgical colorectal cancer patients. We used the Mann-Whitney U test and the Kruskal-Wallis test when appropriate to compare independent groups.Results: Patients with higher Anger Expression-Out had lower natural killer cell numbers than patients with lower Anger Expression-Out (p value = 0.008). No relation was found between natural killer cell levels and Anger State, Anger Trait, or Anger Expression-In. No difference in natural killer cell count was found between patients with and without clinical anxiety or depression.Discussion: These results suggest that, in colorectal cancer patients, natural killer cell counts are influenced by Anger Expression-Out, but not by clinical anxiety or depression.Conclusion: The unregulated emotional expression might be a conditioning factor of innate immunity. Additional studies are needed to further investigate this relation and to ascertain the clinical impact of therapeutic interventions regarding emotional regulation on the anti-tumoral immune response.

scholarly journals Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenzhen Hui ◽  
Jiali Zhang ◽  
Yu Zheng ◽  
Lili Yang ◽  
Wenwen Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Cell ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Critical Role ◽  
Interleukin 2 ◽  
Treg Cells ◽  
Single Cell Sequencing ◽  
Colorectal Cancer Patients

Regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance and tumor evasion. However, the relative low proportion of these cells in peripheral blood and tissues has hindered many studies. We sought to establish a rapamycin-based in vitro Treg expansion procedure in patients diagnosed with colorectal cancer and perform single-cell sequencing to explore the characteristics of Treg cells. CD25+ cells enriched from peripheral blood mononuclear cells (PBMC) of colorectal tumor patients were cultured in X-VIVO15 medium, supplemented with 5% human AB serum, L-glutamine, rapamycin, interleukin-2 (IL-2), and Dynabeads human Treg expander for 21 days to expand Tregs. Treg cells with satisfactory phenotype and function were successfully expanded from CD4+CD25+ cells in patients with colorectal cancer. The median expansion fold was 75 (range, 20–105-fold), and >90.0% of the harvest cells were CD4+CD25+CD127dim/− cells. The ratio of CD4+CD25+Foxp3+ cells exceeded 60%. Functional assays showed that iTregs significantly inhibited CD8+T cell proliferation in vitro. Single-cell sequencing showed that the transcriptome of pTreg (CD4+CD25+CD127dim/− cells isolated from PBMC of colorectal cancer patients) and iTreg (CD4+CD25+CD127dim/− cells expanded in vitro according to the above regimen) cells were interlaced. pTregs exhibited enhanced suppressive function, whereas iTregs exhibited increased proliferative capacity. TCR repertoire analysis indicated minimal overlap between pTregs and iTregs. Pseudo-time trajectory analysis of Tregs revealed that pTregs were a continuum composed of three main branches: activated/effector, resting and proliferative Tregs. In contrast, in vitro expanded iTregs were a mixture of proliferating and activated/effector cells. The expression of trafficking receptors was also different in pTregs and iTregs. Various chemokine receptors were upregulated in pTregs. Activated effector pTregs overexpressed the chemokine receptor CCR10, which was not expressed in iTregs. The chemokine CCL28 was overexpressed in colorectal cancer and associated with poor prognosis. CCR10 interacted with CCL28 to mediate the recruitment of Treg into tumors and accelerated tumor progression. Depletion of CCR10+Treg cells from tumor microenvironment (TME) could be used as an effective treatment strategy for colorectal cancer patients. Our data distinguished the transcriptomic characteristics of different subsets of Treg cells and revealed the context-dependent functions of different populations of Treg cells, which was crucial to the development of alternative therapeutic strategies for Treg cells in autoimmune disease and cancer.

scholarly journals HLA-Cw polypmorphism and killer cell immunoglobulin-like receptor (KIR) gene analysis in Korean colorectal cancer patients

2014 ◽  
Vol 12 (8) ◽  
pp. 815-820 ◽  
Author(s):  
Hyung-Jin Kim ◽  
Hae-Baeg Choi ◽  
Jung-Pil Jang ◽  
In-Cheol Baek ◽  
Eun-Jeong Choi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Killer Cell ◽  
Gene Analysis ◽  
Colorectal Cancer Patients ◽  
Kir Gene
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