Autologous mixed lymphocyte reaction in the peripheral blood and pleural effusions of cancer patients.

Uchida, Atsushi; Micksche, M.

doi:10.1172/jci110608

Cited by 22 publications

(12 citation statements)

References 25 publications

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“…The administration o f IFN -a re sulted in significant increases o f these re sponses which may be explained by the in vivo increase o f H L A -D R molecules which have repeatedly been shown to regulate T-cell activation and proliferation in vitro [17][18][19][20][21], Recent data produced in our laboratory sug gest a decreased expression o f H L A -D R anti gens on monocytes from patients with meta static cancer [23]. These findings along with the information that already exists for the deficient T-cell responses in patients with cancer [23][24][25][26] [4,5,27], it was not clear whether they would exhibit similar increases after therapy in vivo. Fac tors such as rapid clearance o f IFN from the circulation [27] or migration o f affected cells into the tissues [3,28] would prevent in creases from being observed.…”

Section: Discussionmentioning

confidence: 94%

“…Decreases in M L R responses or cytokine production have been noted in patients with autoimmune diseases and cancer [ 13,24,29], Thus, monitoring T-cell responses in the M L R or quantitating IL-2 and IL-1 produc tion may be a sensitive indicator for changes in immune functions and therefore potential ly useful when treating patients with immunomodulating agents. Regardless o f whether IF N treatment causes tumor regression direct ly or via potentiation o f cellular immune responses via T-cell proliferative response and/or cytokine production, it is evident that these immune parameters could be used to determine the biological effect o f IFN -a2b in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

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The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

Tsavaris¹,

Baxevanis²,

Kosmidis³

et al. 1995

Tumor Biol

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We evaluated the response rate and the immunorestorative properties of subcutaneously administered in-terferon-α_2b (IFN- α_2b ) in patients with advanced renal cell carcinoma (RCC) and melanoma (MEL) and correlated the immune status with clinical responses. Thirty-five patients with advanced RCC and 12 with MEL were treated with re-combinant IFN- α_2b The dose was increased progressively from 5 × 10⁶ IU the first week to 10 × 10⁶ IU the second week and thereafter 15 × 10⁶ IU subcutaneously. The response rate for RCC patients was as follows: (1) 6 patients achieved partial responses; (2) 9 patients had stable disease, and (3) 20 patients progressed. The response rate for patients with MEL was as follows: (1) 4 patients experienced partial response and (2) 8 patients progressed. In all patients blood was withdrawn prior to IFN treatment and then monthly. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and allogeneic mixed lymphocyte reaction (allo-MLR), interleukin-2 production (IL-2prod), expression of IL-2 receptors (IL-2rec) during the allo-MLR, and interleukin-1 production (IL-lprod) by peripheral blood monocytes. Striking increases were demonstrated in all parameters 1 month after treatment with IFN- α_2b. Patients with RCC experiencing a partial response showed a mean increase of 50% in the auto-MLR, 95% in the allo-MLR, 62% IL-2prod, 88% IL-2rec and 76% in IL-lprod. Patients with MEL presenting with a partial response showed a mean increase of 70% in the auto-MLR, 91% in the allo-MLR, 97% IL-2prod, 78% IL-2rec and 118% in the IL-lprod. On the contrary, the nonresponders had a decrease in the examined parameters, and in some, deterioration of the already depressed immunologic functions was observed. Therefore, in nonresponders with RCC the auto-MLR was decreased -23%, the allo-MLR -32%, IL-2prod -28%, IL-2rec -25% and IL-lprod -22%. In nonresponders with MEL the auto-MLR was decreased -22%, the allo-MLR -33%, IL-2prod -29%, IL-2rec -25% and IL-lprod -28%. Administration of IFN- α_2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC and MEL who respond to the treatment. On the contrary, the nonresponders demonstrated a decrease in the examined parameters and in some, deterioration of the already depressed immunologic functions was observed. Administration of IFN- α_2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC or MEL who respond to the treatment. This may have prognostic significance, and certainly more patients are required to be studied for definite conclusions.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

Tsavaris¹,

Baxevanis²,

Kosmidis³

et al. 1995

Tumor Biol

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“…Many of these studies reported only abnormalities in the AMLR, but in the case of patients with SLE and AMLR was examined in detail with regard to the etiology of functional disturbance of CD4' suppressor T cells (Sakane et al, 1983;Takada et al, 1985;Morimoto et al, 1987) or the 2H4 molecule on the CD4' T cells (Takeuchi et al, 1988). On the other hand, a defective AMLR was also demonstrated in various malignant conditions (Indiveri et al, 1983;Uchida and Micksche, 1982;Indiveri et al, 1986;Raziuddin et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients

Itō¹,

Tanimura²,

Yamaue³

et al. 1992

Intl Journal of Cancer

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The autologous mixed lymphocyte reaction (AMLR) and the killer activity generated in the AMLR (AMLR-killer) in the spleen and the peripheral blood of patients with gastric cancer were investigated. The AMLR in cancer patients was suppressed, especially in the spleen, compared to that seen in controls. There was no correlation between AMLR activity and the stage status of the cancer. The cytotoxic activity of AMLR-killer cells against various tumor-cell lines was also suppressed in the spleen, and had a tendency to be suppressed in the peripheral blood of cancer patients. The autologous tumor-killing activity of AMLR-killer cells was developed in cancer patients with high AMLR activity, but was not induced in patients with low AMLR activity. Autotumor killing activity was decreased by the elimination of CD4+ cells, whereas the elimination of CD16+ cells resulted in a marked reduction in cytotoxicity against K562, indicating that the non-specific killer cells which lysed K562 were different from the specific killer cells that lysed autotumor cells. This suggests that AMLR activity is related to the differentiation and proliferation of lymphocytes with specific or non-specific cytotoxic activity and that this activity plays an important role in immune surveillance against tumors.

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“…The proliferative response of lymphocytes in autologous MLTC was measured in a 3H thymidine incorporation assay, as described previously [17,21]. Briefly, 1 x 105 lymphocytes were cultured alone or with 2 x 10 4 mitomycin C-treated autologous tumour cells in a total volume of 0.2 ml in wells of microtiter places (Costar) for 6 days at 37 °C in a humidified 5% CO 2 atmosphere.…”

Section: Effusion Tumour Cellsmentioning

confidence: 99%

Lysis of fresh human tumour cells by autologous tumour-associated lymphocytes: Two distinct types of autologous tumour killer cells induced by co-culture with autologous tumour

Uchida

Moore

1985

Cancer Immunol Immunother

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The specific and natural killer (NK)-restricted nature of auto-tumour cytotoxicity of tumour-associated lymphocytes was studied in cancer patients with malignant pleural effusions. Large granular lymphocytes (LGL) and small T lymphocytes were isolated from carcinomatous pleural effusions by centrifugation on discontinuous Percoll gradients. Tumour cells freshly isolated from pleural effusions were classified according to their susceptibility to lysis by Percoll-purified LGL from the blood of normal donors in a 4-h 51Cr release assay. Of 12 NK-sensitive tumour samples, 11 were killed by autologous fresh effusion LGL, whereas only 2 were lysed by autologous T cells. Neither LGL nor T cells were cytotoxic to NK-resistant autologous tumour cells. T cells and LGL were each cultured in vitro with autologous tumour cells for 6 days. Effusion LGL maintained their auto-tumour killing activity in 10 of 12 autologous mixed lymphocyte-tumour cultures (MLTC) with NK-sensitive tumour, while LGL lost the activity when cultured alone. Removal of high-affinity sheep erythrocyte-rosetting cells from Percoll-purified LGL enriched effector cells. Autologous MLTC-derived LGL could also kill NK-sensitive allogeneic effusion tumour cells and K562 cells, as did fresh LGL. In autologous MLTC LGL failed to acquire lytic function to NK-resistant autologous tumour cells. In contrast, in vitro activation of effusion T cells with autologous tumour cells induced auto-tumour killer cells in 9 of 12 NK-sensitive tumour samples and 3 of 6 NK-resistant tumour cases. However, cultured T cells were incapable of killing allogeneic tumour cells and K562 cells. In the autologous MLTC effusion T cells proliferated vigorously in response to autologous tumour cells, whereas LGL showed no proliferation. The enrichment of blasts from cultured T cells on discontinuous Percoll gradients resulted in an enhancement of auto-tumour cytotoxicity, with no reactions recorded in blast-depleted, small, resting T cells. These results indicate that two distinct types of auto-tumour-recognising lymphocytes, LGL and T cells, are present in carcinomatous pleural effusions of cancer patients and that each effector type recognises different membrane moieties of autologous effusion tumour cells.

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Autologous mixed lymphocyte reaction in the peripheral blood and pleural effusions of cancer patients.

Cited by 22 publications

References 25 publications

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients

Lysis of fresh human tumour cells by autologous tumour-associated lymphocytes: Two distinct types of autologous tumour killer cells induced by co-culture with autologous tumour

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Autologous mixed lymphocyte reaction in the peripheral blood and pleural effusions of cancer patients.

Cited by 22 publications

References 25 publications

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-&alpha;<sub>2b</sub>

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-&alpha;<sub>2b</sub>

Defective autologous mixed lymphocyte reaction (AMLR) and killer activity generated in the AMLR in cancer patients

Lysis of fresh human tumour cells by autologous tumour-associated lymphocytes: Two distinct types of autologous tumour killer cells induced by co-culture with autologous tumour

Contact Info

Product

Resources

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The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>

The Prognostic Significance of Immune Changes in Patients with Renal Cancer and Melanoma Treated with Interferon-α<sub>2b</sub>