Biomedical subjects

T J Eberlein

Publications and source records attributed to T J Eberlein.

At least 73 records · Page 4Linked to original sources

PubMed1993

T cell receptor V beta 2 and V beta 6 mediate tumor-specific cytotoxicity by tumor-infiltrating lymphocytes in ovarian cancer.

The interaction between T lymphocytes and the Ag-HLA complex on tumor cells is mediated by the TCR. The diversity and the specificity of the TCR are in part secondary to the gene rearrangement of the V region on the beta-chain (V beta). To determine whether a restricted number of TCR V beta genes are utilized in the recognition of ovarian cancer, tumor-infiltrating lymphocytes (TIL) were isolated from six consecutive untreated ovarian cancer patients. TIL were also cultured using repeated autologous tumor stimulation, and by 7 wk, five of six patients produced bulk cultures consisting of > 50% CD8+ T cells and demonstrating an autologous tumor-specific pattern of cytotoxicity. TCR V beta gene usage was analyzed in the five patients yielding fresh TIL and corresponding 7-wk cultured, tumor-specific TIL; 22 primers specific for 20 TCR V beta gene families were employed and amplified by polymerase chain reaction and then quantitated by HPLC. A heterogeneous pattern of V beta usage was seen in the fresh TIL; however, V beta 2, V beta 3, V beta 6, V beta 7, V beta 8, and V beta 13.1 were found in increased proportions in at least three of five patients. In the 7-wk tumor-specific TIL, V beta analysis showed an increased usage of V beta 2, V beta 3, V beta 6, and V beta 7 in more than three of five patients. No significant change in V beta representation was seen in control populations that were not stimulated with tumor. Looking at the percent change in V beta usage between fresh and 7-wk tumor-specific cultures, V beta 2 and V beta 6 were augmented significantly in at least three of five patients (108% and 61%, respectively). To verify that the increase in representation of these V beta families was responsible for the increased cytotoxicity observed, mAb specific for V beta 2 and V beta 6 were used to block tumor lysis. Anti-V beta 6 and anti-V beta 2 significantly blocked cytotoxicity against autologous tumor cells in those TIL populations expressing increased levels of these V beta families. These data suggest that a selective repertoire of TCR V beta genes is used to recognize the Ag-HLA class 1 complexes on the surface of ovarian tumor cells, and specifically V beta 2 and V beta 6 appear to mediate antitumor activity. These findings may aid in the development of a more specific immunotherapy in ovarian cancer.

Antibodies, Monoclonal↗

PubMed1993

HLA-A2 presents shared tumor-associated antigens derived from endogenous proteins in ovarian cancer.

Tumor-associated lymphocytes (TAL) from the malignant ascites and tumor-infiltrating lymphocytes (TIL) from the solid tumor were isolated from six consecutive untreated ovarian cancer patients. Tumor-specific CTL were generated from both TAL and TIL using solid phase anti-CD3, low dose IL-2 (50 IU/ml), and repeated tumor stimulation. The specificity of TAL and TIL was tested in standard cytotoxicity assays using autologous tumor, several allogeneic ovarian tumors, and the NK-sensitive cell line, K562. Anti-HLA-A-B-C mAb, W6/32, was used to demonstrate that these tumor-specific TAL and TIL were HLA class I-restricted. The ability of the ascitic and solid tumor to present Ag by HLA class I was assessed using Brefeldin A, a fungal metabolite that blocks the endogenous Ag-processing pathway in the viral model. Brefeldin A significantly inhibited tumor-specific cytotoxicity as well as HLA class I expression on the cell surface, suggesting an endogenous source of tumor-associated Ag. Despite previous reports of antigenic heterogeneity in ovarian cancer, shared tumor-associated Ag were shown to exist in this disease as demonstrated by significant allogeneic recognition of HLA-A2-matched patients as opposed to unmatched controls. Specifically, CTL from HLA-A2+ patients lysed HLA-A2+ allogeneic targets significantly better than HLA-A2- allogeneic or HLA-A2+ melanoma targets. There was no such difference with HLA-A2- effectors. Furthermore, HLA-A2 was confirmed to be a major restriction element in ovarian cancer by the blocking of HLA-A2+ effectors against both autologous and allogeneic HLA-A2+ targets with the anti-HLA-A2 mAb, BB7.2. These findings verify a similar lymphocyte/tumor interaction as has been documented in melanoma, suggesting a common mechanism of recognition of these human tumors by lymphocytes.

Antigen Presentation↗

PubMed1993

The influence of angiogenesis inhibitor AGM-1470 on immune system status and tumor growth in vitro.

The synthetic angiogenesis modulator-1470 O-(chloroacetyl-carbamoyl, AGM-1470) is a potent inhibitor of neovascularization. We have investigated the potential influence of this inhibitor in tumor immunobiology using both in vivo and in vitro models. Mice given a single tail-vein injection of tumor cells were later treated wtih AGM-1470 by s.c. injection. After tumor injection, the lungs were evaluated for macroscopic tumor nodules. AGM-1470 significantly reduced the development of macroscopic pulmonary disease but did not eliminate disease. However, tumor-bearing mice treated with AGM-1470 had significantly reduced spleen weight compared to controls. To determine if the observed decrease in spleen weight in the treated animals was associated with immunosuppression, we studied the possible immunomodulatory effects of AGM-1470. AGM-1470 induced no changes in spleen-cell viability compared to controls. However, addition of angioinhibin at the beginning of IL-2-induced spleen-cell activation significantly inhibited the development of NK-mediated tumor-cell killing. Similarly, splenic T-cell proliferation induced by a mitogenic monoclonal antibody to murine T cells was significantly inhibited when activated in the presence of AGM-1470. The in vitro studies were extended by evaluation of immune system status in tumor-bearing mice treated with AGM-1470. In vivo therapy with AGM-1470 did not significantly change the mean splenic lymphocyte counts and CD4/CD8 ratios from control values. In addition, the induction of splenic NK-mediated tumor killing with IL-2 as well as mitogen-induced T-cell activation was not significantly different from control values. These results suggest that AGM-1470 inhibits tumor growth by blocking neovascularization and may, under certain conditions of drug administration, inhibit immune system function.

Animals↗

PubMed1993

CD4+ T cell clones isolated from human renal cell carcinoma possess the functional characteristics of Th2 helper cells.

The underlying cause for the observed poor antitumor activity of lymphocytes resident, in situ, in freshly resected human renal cell carcinoma (RCC) is unknown. To examine the basis for this observation we evaluated 217 T cell clones established from 20 consecutive patients with renal cell carcinoma. Of these, 75% were CD4+, 22% were CD8+, and 3% were NK+. Cytotoxic T cell function of CD4+ and CD8+ T cell clones was assessed by antibody-induced triggering of the TcR/CD3 complex. Nearly 93% of the CD4+ clones possessed poor cytolytic activity defined as < 50% killing (E:T, 50:1). Alternatively, nearly 80% of CD8+ clones possessed strong cytolytic activity defined as > or = 50% killing. In all T cell clones tested, MHC nonrestricted killing against Daudi or K562 was not observed. Overall, 77% of the T cell clones isolated from patients with RCC in this study were characterized by poor antitumor cytotoxic function; only 22% of the clones displayed strong cytolytic activity. Clones with strong cytotoxic function were tested for cytotoxic function against autologous tumor. However, all clones tested demonstrated little to no tumoricidal activity against autologous tumor. These results indicate that cytolytic T cells, while present in RCC, are not effectively activated by tumor to express CTL function. The immunobiology of CD4+ T cell clones was further evaluated. Thirty-two CD4+ clones from seven patients revealed distinct patterns of cytokine production following TcR/CD3 activation. CD4+ clones could be divided into IL-2 nonproducers and IL-2 producers. A total of 27/32 clones did not produce IL-2 following activation and IFN-gamma production by IL-2 nonproducers was more than threefold less than that by IL-2 producers. However, no differences were found in the levels of IL-4, IL-6, GM-CSF, or TNF-alpha between the two groups. Antitumor cytotoxicity mediated by CD4+ clones did not correlated with cytokine production. These results demonstrate that among T cells resident in human RCC, the predominant type of lymphocyte population consists of noncytolytic helper CD4+ T cells capable of secreting IL-4, but importantly not IL-2, and low levels of IFN-gamma following activation, thus resembling murine Th2 cells. Only a minor contribution by Th0-like cells was observed (i.e., CD4+ clones capable of secreting IL-2, IL-4, and IFN-gamma following activation).(ABSTRACT TRUNCATED AT 400 WORDS)

CD4-Positive T-Lymphocytes↗

PubMed1993

Survival characteristics of metastatic renal cell carcinoma patients treated with lymphokine-activated killer cells plus interleukin-2.

The immunologic manipulation of patients with metastatic renal cell carcinoma using lymphokine-activated killer (LAK) cells in conjunction with systemic interleukin-2 (IL-2) has been examined under conditions in which the life-threatening toxicities associated with IL-2 treatment have been virtually eliminated. We have examined tumor regression in vivo as well as the survival characteristics of 12 patients with metastatic renal cell carcinoma following immunotherapy. Five of 12 (42%) patients experienced tumor regression exceeding 50 percent following treatment. To determine if immunotherapy had influenced the length of survival, all patients were followed until the time of death. Previous studies have characterized the length of survival of metastatic renal cell cancer patients according to a combination of risk factors unique for each patient. In this model, patients were categorized into risk groups based on the number of risk factors. Survival was found to be dependent on risk factors such as performance status, time from initial diagnosis, number of metastatic sites, recent weight loss, and prior cytotoxic chemotherapy. On completion of the LAK cell immunotherapy protocol, patients were categorized as nonresponders or responders. In addition, they were assigned to risk groups based on their unique profile of risk factors at the time of entry into the protocol. Using this model, we found the median survival of nonresponders (23 months) to be no different from responders (24 months), p > 0.05. This was directly attributable to differences in risk factors which characterized members in these two response groups. However, the observed median survival of nonresponders following therapy was 1.9-fold longer than their projected survival based on the risk factors. Furthermore, the observed median survival of responders was 3.4-fold longer than projected from their risk factors. These results suggest that regardless of response status to therapy, cellular immunotherapy may play a role in mediating a significant palliative effect on the metabolic characteristics of these patients leading to extended survival.

Carcinoma, Renal Cell↗

PubMed1993

Prospective evaluation of immediate reconstruction after mastectomy.

OBJECTIVE: The authors prospectively studied the impact of immediate breast reconstruction on patients undergoing mastectomy. SUMMARY BACKGROUND DATA: Despite the advocation of a breast-conserving approach to the treatment of breast cancer, many women continue to medically require or choose mastectomy for the treatment of breast cancer. In recent years, immediate breast reconstruction has become an alternative to either mastectomy alone or to delayed reconstruction. METHODS: A prospective database of 216 patients who underwent mastectomy with immediate reconstruction was established. In this series, 94 procedures involved implants or tissue expanders, and 124 tissue transfers were performed. RESULTS: The overall complication rate was 15.3%; only 9% of patients who underwent autologous tissue transfers required secondary procedures. When implants were performed, the overall rate of prosthetic loss was 8%. The majority of patients (n = 101) underwent transverse rectus abdominis musculocutaneous (TRAM) flaps. Twenty-six of the 38 (17.5%) patients who required transfusion were from this group. Partial flap losses in this group (7%) were correlated to a history of heavy smoking. With a median follow-up of 33.2 months, only two patients had recurred locally. According to patient opinion, autologous tissue transfers resulted in a statistically better cosmetic result. CONCLUSIONS: Immediate reconstruction can be performed safely and with excellent cosmetic results.

Adult↗

PubMed1993

Immunomodulatory effects of interleukin-12 on human tumor-infiltrating lymphocytes.

Interleukin (IL)-12 is a recently described cytokine with multiple immunoregulatory effects on various lymphoid populations, including peripheral blood lymphocytes (PBL), natural killer (NK) cells, and T-cell subsets. We examined the effects of recombinant IL-12 on the immune function of human tumor infiltrating lymphocytes (TIL) from several different tumor types. At an optimal concentration of 50 IU/ml, IL-12 acted as a co-stimulant for TIL recently activated with anti-CD3 antibodies, giving stimulation indices between 2.6 and 9.9. This co-stimulatory effect was independent of IL-2 and was not inhibited by neutralizing antibody to human IL-2. When IL-2 and IL-12 were used synchronously as co-mitogenic stimuli in culture with activated TIL, the effect on proliferation was additive. This additive effect held true over a range of suboptimal concentrations of IL-2 and in different TIL populations. IL-12 did not enhance non-major histocompatibility complex (MHC)-restricted cytotoxicity in the TIL populations tested. TIL cultured with IL-12 killed more autologous tumor targets than TIL maintained in media alone at identical effector/target (E/T) ratios. This effect on cytotoxicity was not as great as that seen in TIL maintained in low-dose IL-2. Co-culture with IL-12 did not change the phenotype of TIL used in these assays. The importance of these findings and possible uses in immunotherapy are discussed.

Adjuvants, Immunologic↗

PubMed1993

T-cell recognition of ovarian cancer.

BACKGROUND: The existence of a tumor-specific T-cell immune response to human malignant melanoma has been well documented. In contrast, the existence of tumor-specific cytotoxic T lymphocyte to ovarian cancer remains controversial despite the abundant lymphocytic infiltrates in the malignant ascites and solid tumor of these patients. METHODS: Tumor-associated lymphocytes (TAL) from the malignant ascites and tumor-infiltrating lymphocytes (TIL) from the solid tumors were isolated from six untreated patients with ovarian cancer. TAL and TIL were grown with initial anti-cluster of differentiation of T cells (CD3), low-dose interleukin-2, and tumor stimulation. T-cell lines were analyzed in functional studies. RESULTS: At 5 weeks, TAL and TIL from five of six patients were > 50% CD8+, and one of six was > 70% CD4+. In all five pairs of CD8 positive cultures, both TAL and TIL exhibited high levels of tumor-specific cytotoxicity for ascite and solid tumor, respectively. T-cell recognition of tumor was mediated through the T-cell receptor-CD3 complex and was human leukocyte antigen class I restricted. TAL and TIL lysed autologous ascitic tumor equally well; however, TAL-mediated tumoricidal activity against autologous solid tumor was consistently and significantly poorer than TIL-mediated killing. CONCLUSIONS: Tumor-specific cytotoxic T lymphocytes can be expanded from both TAL and TIL. However, TAL do not kill solid tumor as efficiently as TIL. This suggests the requirement of TIL, or a combination of TIL and TAL, for effective immunotherapy.

Adult↗

PubMed1993

Dextrocholedocholithiasis: calculous obstruction complicating double ductus choledochus in an adult.

Double ductus choledochus is a rare anomaly of the extrahepatic biliary tree in which the common bile duct is represented by two independent hepatic ducts. Patients with this abnormality may have unimpeded biliary drainage and remain symptom free, yet various forms of double ductus choledochus are occasionally encountered in patients undergoing operation for symptomatic cholelithiasis. We describe a patient in whom doubled biliary ducts were identified on exploration for cholecystectomy along with calculous obstruction of the right-sided duct (ductus choledochus dextri). This case illustrates the potential for significant injury to the biliary tree when double ductus choledochus is present. In addition to a means by which to manage this problem at the time of operation, a review of the literature, as well as a description of this rare embryologic abnormality, is presented.

Adult↗

PubMed1992

Long-term salvageability for patients with locally recurrent soft-tissue sarcomas.

Between 1971 and 1988, 39 patients were referred because of local recurrence of soft-tissue sarcomas and data from their patient records were analyzed to determine the parameters governing local recurrence. Mean follow-up was 11.1 years, with a mean time to local recurrence of 22 months. Twenty-one patients had local recurrence only, without metastatic disease. Salvage was provided for 14 (67%) of these patients after reexcision of local recurrence, and all 14 patients remained free of disease (mean follow-up, 112 months). We conclude that (1) excisional biopsy of tumors larger than 3 cm leads to potential contamination of clean tissue planes, limits ability to achieve an adequate margin of resection, and may compromise the definitive excision, and (2) in patients with local recurrence only, there is a high rate of long-term salvage (67% for follow-up of 9.3 years) after radical compartmental excision with or without postoperative radiation therapy.

Adolescent↗

PubMed1992

Benign schwannoma of the esophagus presenting as a giant fibrovascular polyp.

The case of a 62-year-old man with benign schwannoma associated with a giant polyp of the esophagus is presented. His initial symptom was dysphagia. The polyp was removed through cervical esophagotomy. He had no recurrence of symptoms 5 years after this procedure. Pathologic examination showed a rare histology.

Esophageal Neoplasms↗

PubMed1992

Secondary cytokine production by lymphoid cells used in cellular immunotherapy.

Interleukin-2 (IL-2) has been used extensively in cellular immunotherapy trials as a systemic activator of the immune system as well as an ex vivo stimulant for lymphoid cell function. Despite the measurement of several in vitro and in vivo immunologic parameters related to cellular immunotherapy, determinants of successful cellular immunotherapy remain unknown. To further delineate the consequences of exposing peripheral blood lymphocytes to high concentrations of IL-2, we assessed the supernatants of IL-2-activated peripheral blood lymphocytes for production of tumour necrosis factor (TNF) and interferon-gamma (IFN-gamma). Exposure of normal monocyte-depleted peripheral blood mononuclear cells (PBMC) to IL-2 caused a dose-dependent increase in secretion of TNF and IFN-gamma which increased linearly after 48 h in culture. Analysis of positively selected, highly purified PBMC subpopulations exposed to IL-2 revealed that TNF-alpha and TNF-beta were produced by both CD3+ and CD16+ subpopulations but not by CD22+ cells. These studies were extended to supernatants obtained from PBMC cultures used in the adoptive cellular immunotherapy of patients with advanced cancer. Patients treated with lymphokine-activated killer (LAK) cell immunotherapy were classified as responders (N = 14) or non-responders (N = 17) to therapy. We found no significant difference in the production of TNF between responders and nonresponders (22 +/- 9 U ml-1 vs. 20 +/- 6 U ml-1), P > 0.05. However, LAK cell supernatants harvested from non-responders contained a significantly higher level of IFN-gamma (232 +/- 94 U ml-1) compared with responders (42 +/- 14), P < 0.05. Furthermore, the linear association between IFN-gamma and TNF-alpha production was different between these two response groups (rs = -0.19 for non-responders and rs = 0.48 for responders). These results suggest that secondary cytokine production by adoptively transferred lymphocytesmay play an important role in the host response to cellular immunotherapy.

Cells, Cultured↗

PubMed1992

The biological effects of immunosuppression on cellular immunotherapy.

Cytoreductive chemotherapy and immunosuppression have been postulated as possible adjuncts to cancer immunotherapy in studies using murine tumour-infiltrating lymphocytes (TIL). Treatment of animals with cyclophosphamide (Cy) therapy alone caused two distinct biological activities that altered the relationship between host and tumour. These two in vivo activities were distinguished by altering the timing and dose of Cy administration relative to tumour implantation. Cy administered 3 days following tumour injection caused a significant decline in the number of pulmonary micrometastases and greater survival compared to untreated controls in proportion to the dose of Cy administered. Further reduction in pulmonary disease was observed when Cy-treated mice were given TIL therapy. The possible role(s) of Cy-induced immunosuppression was studied by injecting Cy 24 h prior to tumour injection. This treatment failed to cause the cytoreductive effect observed when Cy was administered 3 days after tumour since Cy-administration prior to tumour resulted in a significantly higher number of pulmonary metastases and diminished survival compared to untreated controls. Despite the increased number of pulmonary metastases and decreased survival in mice treated with Cy before administration of tumour, therapy with TIL significantly diminished pulmonary disease compared to animals treated with Cy alone. Immunosuppression (without concomitant cytoreductive therapy) prior to TIL treatment significantly prolonged survival. Additional studies with TIL therapy indicate that the survival of animals immunosuppressed prior to tumour injection was significantly longer than controls which received immunotherapy alone. These results suggest that the combustion of immunosuppression plus cellular immunotherapy, which leads to significant survival advantage in these murine tumour models, may possibly augment the clinical response in human TIL trials.

Animals↗

PubMed1992

Evaluation of the contralateral breast. The role of biopsy at the time of treatment of primary breast cancer.

Ninety-five women who underwent blind contralateral breast biopsy during surgical treatment of a known breast cancer primary were studied prospectively. All biopsies were performed between 1981 and 1989. Patients with palpable or mammographic abnormalities prompting the contralateral biopsy were excluded so that the study sample included only truly blind contralateral biopsies. Only two infiltrating carcinomas were found, resulting in a positive biopsy rate of 2.1% for invasive disease. Three additional biopsies showed only lobular carcinoma in situ, a finding that usually does not alter clinical management. One patient with a negative contralateral biopsy developed invasive carcinoma in that breast within 2 years of the biopsy. The authors were unable to identify any subgroup of patients at increased risk of a positive contralateral biopsy. These results suggest that blind biopsy of the contralateral breast performed at the time of the initial treatment of breast carcinoma is not an efficient method of cancer detection. Alternative management strategies are discussed.

Adult↗

PubMed1991

The systemic complement activation caused by interleukin-2/lymphokine-activated killer-cell therapy of cancer causes minimal systemic neutrophil activation.

Twenty-three cancer patients undergoing therapy with interleukin-2 and lymphokine-activated killer cells were studied for evidence of complement activation and systemic neutrophil activation occurring during the course of therapy. Patient plasma samples demonstrated evidence of marked complement activation, with 3-fold elevations of C3a desArg concentrations by the 8th day of therapy. Concentrations of C4a desArg were also elevated by the end of therapy. In vitro chemotaxis of patients' neutrophils both to C5a and to the synthetic peptide chemotaxin, FMLP, was initially normal and then fell progressively to 60% of normal by the end of treatment. Mean neutrophil cell-surface expression of complement receptor Type 1 and complement receptor Type 3 increased in inverse temporal relationship to the deficit in chemotaxis, but showed no consistent pattern for individuals and was only doubled at maximum. Thus, despite a degree of complement activation which should have produced pronounced neutrophil activation, the response of the circulating neutrophils was diminished. In view of this discrepancy, the toxicity of this therapy may not be mediated by activation of circulating neutrophils.

Chemotaxis, Leukocyte↗

PubMed1991

Results of radical radiotherapy for inflammatory breast cancer.

We performed a retrospective review of 65 patients with nonmetastatic clinical inflammatory breast carcinoma treated with radical radiotherapy as the sole local treatment between 1968 and 1986. Chemotherapy was given to 47 patients (72%). The median total radiation dose to the target volume was 6,984 cGy. With a median follow-up in survivors of 41 months, the 5-year actuarial probability of relapse-free survival was 17% and the overall survival was 28%. Thirty patients experienced failure in the treated breast, skin, or draining lymph nodes, for a crude, uncensored local recurrence rate of 46%. Of the factors analyzed, only the response to initial chemotherapy was predictive of local recurrence. Local recurrence was noted in 0 of 3 patients with a complete response (CR) to initial chemotherapy, 5 of 17 patients with a partial response (PR), and 12 of 17 patients with less than a partial response (CR/PR versus less than PR, p = 0.009). We conclude that conventional radical radiotherapy in unselected patients is insufficient to manage the local tumor burden presented by inflammatory breast cancer, even when high doses are employed.

Actuarial Analysis↗

PubMed1991

The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.

Breast Neoplasms↗

PubMed1991

Approaches to immunotherapy of cancer: characterization of lymphokines as second signals for cytotoxic T-cell generation.

Lymphokines, the soluble molecules produced by cells of the immune system, regulate cell-cell interactions and, consequently, the functional status of the immune system. Altering immunoregulatory pathways with lymphokines in vivo may provide a mechanism for controlling a variety of immunologic disorders. Although normally produced in vivo in very small quantities, the widespread availability of recombinant lymphokines has made it possible to study the molecular signals involved in production of lymphocyte effectors with activity against tumor. For example, interleukin-2-based cancer immunotherapy programs have, in certain clinical situations, suggested that immunologic intervention can influence the regression of metastatic cancer. Ultimately the successful application of these biologic agents requires an understanding of the interaction between the immune system and tumor on a molecular level. To induce a given biologic effect, it is necessary both to classify the required lymphokines and to identify the relevant effector cell populations. This review will examine the progress made in identifying the requirements for lymphokine-induced cytotoxic T-lymphocyte function.

Humans↗