Suppressor cells in the effector phase of autologous cytotoxic reactions in cancer patients

Eura, Masao; Maehara, Tatsuhiko; Ikawa, Tsutomu; Ishikawa, Takeru

doi:10.1007/bf00200020

Cited by 23 publications

(6 citation statements)

References 23 publications

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“…Inhibition of NK activity mediated by suppressor lymphocytes and monocyte macrophages has been observed in mice during tumor development (Parhar and Lala, 1985;Young et al, 1986). Since unseparated PBLs were used to study NK activity, the suppressor cells present among the PBLs of cancer patients might be responsible for the observed deficient NK activity (Eura et al, 1988). The presence of such suppressor cells in PBLs of elderly healthy men might also explain the deficient NK activity observed in this group compared with that in their younger counterpart (Fig.…”

Section: Discussionmentioning

confidence: 95%

Prolactin response of NK cells, but not of LAK cells, is deficient in patients with carcinoma of oral cavity and during aging

Chakraborty

Chattopadhyay

1996

Int. J. Cancer

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The regulatory role of prolactin (Prl) on peripheral blood natural killer (NK) and lymphokine-activated killer (LAK) cell activities was studied in young (mean age, 40 years) and elderly (mean age, 68 years) healthy men and patients with carcinoma of the oral cavity (oral cancer). The peripheral blood NK cells, but not the LAK cells, were found to be depressed in oral cancer patients compared with age-matched healthy men. However, age-associated deficiency in both NK and LAK cell activity was observed in healthy men and cancer patients. Prl produced dosedependent inhibition (I, 10, 100 or 250 ng/ml) or stimulation (25-50 ng/ml) of resting NK cells in young groups of healthy men and cancer patients. In elderly groups less or no response of the NK cells to low doses of Prl (I-I 0 ng/ml) was evident. The NK cells of young and elderly healthy men were stimulated by human recombinant Interleukin-2 (rlL-2) (100 U/ml), and Prl (1-250 ng/ml) inhibited these cells. In oral cancer patients an altered response to low doses of Prl(1-50 ng/ml) was observed in IL-2-stimulated NK cells, which also revealed malignancyassociated loss of IL-2 response. In contrast, there was no malignancy or age-associated change in Prl response of the LAK cells. Treatment of peripheral blood lymphocytes of both healthy men and oral cancer patients for 5 days with Prl(50 ng/ml) in the presence of low concentration of serum generated LAK cells.o 1996 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 95%

Prolactin response of NK cells, but not of LAK cells, is deficient in patients with carcinoma of oral cavity and during aging

Chakraborty

Chattopadhyay

1996

Int. J. Cancer

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“…LNL are the next most immunosuppressed population of effector cells. Regional LNL have reduced NK and lymphokine‐activated killer (LAK) cell activities, mitogenic responses, and cytokine production when compared with PBL 44,45,72–75 . LNL in closer proximity to the primary tumor bed show weak response to IL‐2 stimulation compared with distally located LNL.…”

Section: Discussionmentioning

confidence: 99%

Covalent linking of proteins and cytokines to suture: Enhancing the immune response of head and neck cancer patients

et al. 2003

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Backgrwund:The immune system of advanced stage head and neck cancer patients is frequently suppressed. Poor immune function has been correlated with poor clinical outcome. Immunotherapeutic strategies have been previously attempted in an effort to enhance immune function and improve survival. Previous studies have shown surgical suture can be transformed into an immune stimulant capable of activating the T lymphocytes of cancer patients. The development of a process for covalently linking proteins and cytokines to suture could have enormous potential for the in vivo manipulation of the immune system. Hypothesis: We hypothesize proteins and cytokines can be covalently linked to surgical suture while preserving their functional properties. Study Design: Prospective study testing normal donor and head and neck squamous cell carcinoma (HNSCC) patient lymphocytes. Method. Polyester suture was acid hydrolyzed followed by reacting with l-ethyl-3(-3-dimethylamino propyl carbodiimide) (EDAC) to create a suture-EDAC intermediate. activity. The optimal conditions for linking 1C2 or m-7 were defined. The covalently linked cytokines retained their immune enhancing properties for stimulating PBL and lymph node lymphocytes (LNL) from HNSCC patients to proliferate, generate a TH1 immunologic profile of cytokines (IG2, IL-12, IFN-y), and stimulate T lymphocytes. Conclusion: This is the first report to demonstrate that cytokines can be covalently linked to surgical sutures and retain their immune-stimulating properties. Proteins linked to suture also retained their enzymatic activity. The clinical implications of functionally active cytokines or proteins linked to surgical suture may be very significant in the future for manipulating the immune system in vivo o r enhancing wound healing.

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“…The fact that a high ASTC CTL frequency was found even among lymphocytes harvested from PIR2-high cell-number LDC wells ( Table 1) also indicates that the suggested suppression is not operative at the level of induction of ASTC cells but rather on their cytotoxic activity at the effector phase; suppression ofthe induction of ASTC would have resulted in a reduced frequency of ASTC CTL among cells harvested from PIR-2 -high cell-number LDC wells. The existence of suppressor cells regulating autologous cytotoxicity at the effector phase has been recently reported in cancer patients (22). In addition, Joly et al (16) recently reported the existence of CD8+ class I-nonrestricted suppressor cells that suppress, at the effector phase, the cytotoxicity against autologous anti-HIV-infected target cells, as well as the activity of antiautologous HLA CTL.…”

Section: Discussionmentioning

confidence: 95%

“…Freshly obtained splenocytes or lymphocytes harvested from 5-d MLC were plated in LDC as previously described (5,18) . Briefly, graded numbers (10-50,000) of responding cells were cultured for 8-9 d in round-bottomed 96-well plates (Nunc) in [16][17][18][19][20][21][22][23][24] replicates, in the presence of 106/well of irradiated (30 Gy) allogeneic splenocytes and human rIL-2 (250 U/ml, Cetus Corp., Emeryville, CA) in a final volume of 0.2 ml complete DME. In some experiments (secondary LDC), the responding cells were obtained from selected LDC wells .…”

Section: Methodsmentioning

confidence: 99%

Cytotoxic T lymphocytes reactive against a syngeneic murine tumor and their specific suppressor T cells are both elicited by in vitro allosensitization.

Leshem¹,

Kedar²

1990

The Journal of Experimental Medicine

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The induction of cytotoxic response against syngeneic or autologous murine or human tumor cells by pool allosensitization in bulk MLC was demonstrated by Bach et al. (1,2). Subsequently, we showed the existence ofmurine cytotoxic cell precursors that can be activated to react with syngeneic tumor cells by single-donor allosensitization in bulk MLC, applying the limiting dilution cultures (LDC) t technique (3, 4). We also showed that a high frequency (1/20) of cytotoxic cells can be elicited in the same manner even against syngeneic, weakly immunogeneic (MT2, mammary carcinoma in C3H mice ; M109, lung carcinoma in BALB/c mice) or nonimmunogenic (PIR-2, x-irradiation-induced lymphoma in 136 mice) tumors (5, 6). We postulated that shared or crossreactive antigenic determinants between the allogeneic leukocytes and the syngeneic tumor cells lead to the elicitation of the antisyngeneic tumor cytotoxic (ASTC) cells. Similar findings were reported by others (7-11) . Recently, we have demonstrated (12) that the ASTC precursors are phenotypically "classical" CTL precursors (i.e., Thy-1' ; Lyt-2+ ; L3T4-; asialo GMl -) rather than classical NK-type lymphokine-activated killer (LAK) cells that might have arisen in the presence of the high concentration of IL-2 (>250 U/ml) in the LDC.In our MLC-LDC system, in which the syngeneic target cells were the syngeneic PIR-2 cells, no ASTC response could be demonstrated by directly testing lymphocytes sensitized in bulk MLC (5, 6). The high ASTC frequency, as well as the antiallotarget response, were demonstrated in LDC wells plated with a low number of MLC-derived responding cells (<200/well). As the number of responding cells plated per well increased beyond a critical number (usually 500/well), a gradual decrease ofASTC response was observed. No anti-PIR-2 cytotoxicity could be detected when >5,000 MLC-derived cells were plated per well in LDC (3-5), whereas the percentage of cytotoxically positive wells against the allotarget, as well as the level of antiallocytotoxicity of the individual wells, remained at maximum .

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Suppressor cells in the effector phase of autologous cytotoxic reactions in cancer patients

Cited by 23 publications

References 23 publications

Prolactin response of NK cells, but not of LAK cells, is deficient in patients with carcinoma of oral cavity and during aging

Prolactin response of NK cells, but not of LAK cells, is deficient in patients with carcinoma of oral cavity and during aging

Covalent linking of proteins and cytokines to suture: Enhancing the immune response of head and neck cancer patients

Cytotoxic T lymphocytes reactive against a syngeneic murine tumor and their specific suppressor T cells are both elicited by in vitro allosensitization.

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