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D S Reintgen

Publications and source records attributed to D S Reintgen.

At least 73 records · Page 4Linked to original sources
PubMed1998

Guidelines for sentinel node biopsy and lymphatic mapping of patients with breast cancer.

OBJECTIVE: To define preliminary guidelines for the use of lymphatic mapping techniques in patients with breast cancer. SUMMARY BACKGROUND DATA: Lymphatic mapping techniques have the potential of changing the standard of surgical care of patients with breast cancer. METHODS: Four hundred sixty-six consecutive patients with newly diagnosed breast cancer underwent a prospective trial of intraoperative lymphatic mapping using a combination of vital blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node (SLN) was defined as a blue node and/or a hot node with a 10:1 ex vivo gamma probe ratio of SLN to non-SLN. All SLNs were bivalved, step-sectioned, and examined with routine hematoxylin and eosin (H&E) stains and immunohistochemical stains for cytokeratin. A cytokeratin-positive SLN was defined as any SLN with a defined cluster of positive-staining cells that could be confirmed histologically on H&E sections. RESULTS: Fine-needle aspiration (FNA) or stereotactic core biopsy was used to diagnose 195 of the 422 patients (46.2%) with breast cancer; 227 of 422 patients (53.8%) were diagnosed by excisional biopsy. The SLN was successfully identified in 440 of 466 patients (94.4%). Failure to identify an SLN to the axilla intraoperatively occurred in 26 of 466 patients (5.6%). In all patients who failed lymphatic mappings, a complete axillary dissection was performed, and metastatic disease was documented in 4 of 26 (15.4%) of these patients. Of the 26 patients who failed lymphatic mapping, 11 of 227 (4.8%) were diagnosed by excisional biopsy and 15 of 195 (7.7%) were diagnosed by FNA or stereotactic core biopsy. Of interest, there was only one skip metastasis (defined as a negative SLN with higher nodes in the chain being positive) in a patient with prior excisional biopsy. A mean of 1.92 SLNs were harvested per patient. Twenty percent of the SLNs removed were positive for metastatic disease in 105 of 440 (23.8%) of the patients. Descriptive information on 844 SLNs was evaluated: 339 of 844 (40.2%) were hot, 272 of 844 (32.2%) were blue, and 233 of 844 (27.6%) were both hot and blue. At least one positive SLN was found in 4 of 87 patients (4.6%) with noninvasive (ductal carcinoma in situ) tumors. A greater incidence of positive SLNs was found in patients who had invasive tumors of increasing size: 18 of 112 patients (16%) with tumor size between 0.1 mm and 1 cm had positive SLNs. However, a significantly greater percentage of patients (43 of 131 [32.8%] with tumor size between 1 and 2 cm and 31 of 76 [40.8%] with tumor size between 2 and 5 cm) had positive SLNs. The highest incidence of positive SLNs was seen with patients of tumor size greater than 5 cm; in this group, 9 of 12 (75%) had a positive SLN (p < 0.001). CONCLUSIONS: This study demonstrates that accurate SLN identification was obtained when all blue and hot lymph nodes were harvested as SLNs. Therefore, lymphatic mapping and SLN biopsy is most effective when a combination of vital blue dye and radiolabeled sulfur colloid is used. Furthermore, these data demonstrate that patients with ductal carcinoma in situ or small tumors exhibit a low but significant incidence of metastatic disease to the axillary lymph nodes and may benefit most from selective lymphadenectomy, avoiding the unnecessary complications of a complete axillary lymph node dissection.

Biopsy↗
PubMed1998

Local recurrence of breast cancer after cytological evaluation of lumpectomy margins.

Successful breast conservation therapy with optimal cosmesis requires adequate tumor excision and negative tumor margins. Therefore, more sensitive techniques are being developed to identify lumpectomy margins intraoperatively with greater accuracy. Unidentified microscopic disease is seemingly responsible for a local recurrence rate of up to 25 per cent 3 to 5 years after lumpectomy and radiotherapy for breast cancer patients. As a result, Moffitt Cancer Center has routinely used an intraoperative touch preparation cytology (TPC) protocol to evaluate the entire resected surface of all lumpectomies. In addition, resection margins were also evaluated by gross examination and by standard histology. In rare instances frozen sections were used to evaluate tumor margins. In this study 701 consecutive lumpectomy specimens were evaluated by TPC during the period of 9 years with a mean follow-up of 3.5 years. Local cancer recurrence was 2.7 per cent (mean recurrence, 2.53 years), in women whose lumpectomy margins were evaluated by TPC. Of interest, a local recurrence rate of 14.6 per cent was observed in patients who had referral lumpectomies evaluated by conventional histopathology. This study suggests that accurate margin assessment with TPC plays an important role in the control of local recurrence after breast conservation therapy. Therefore, we conclude the routine use of intraoperative TPC provides rapid, reliable, topographically accurate identification of residual microscopic disease at lumpectomy margins.

Biopsy↗
PubMed1998

Lymphatic mapping in the treatment of breast cancer.

Developed initially for the treatment of malignant melanoma, lymphatic mapping and sentinel lymph node biopsy have recently been introduced into the treatment of early breast cancer. In breast cancer patients, harvested sentinel lymph nodes are evaluated more thoroughly by detailed pathologic examination using serial sectioning, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. This allows for the detection of smaller tumor volumes and leads to more accurate staging. Lymphatic mapping has a 68% to 98% success rate in identifying the sentinel lymph node. The false-negative rate (defined as a negative sentinel lymph node while a higher node or nodes in the axilla are positive) is between 0% and 2%. The morbidity associated with this procedure is minimal. We believe that lymphatic mapping and sentinel lymph node biopsy will ultimately lead to more conservative treatment of patients with breast cancer. This article describes the historical background and technical aspects of the procedure. This is followed by updated, prospectively collected outcomes data from 466 consecutive breast cancer patients who underwent lymphatic mapping at the H. Lee Moffitt Cancer Center, as well as an up-to-date review of the literature.

Biopsy↗
PubMed1997

Multiple primary melanomas: implications for screening and follow-up programs for melanoma.

BACKGROUND: Once individuals are diagnosed with malignant melanoma, they are at an increased risk of developing another melanoma when compared with the normal population. METHODS: To determine the impact of an intensive follow-up protocol on the stage of disease at diagnosis of subsequent primary melanomas, a retrospective query was performed of an electronic medical record database of 2,600 consecutively registered melanoma patients. RESULTS: Sixty-seven patients (2.6%) had another melanoma diagnosed at the time of presentation to the clinic or within 2 months (synchronous) and another 44 patients (1.7%) developed a second primary melanoma during the follow-up period (metachronous). For the 44 patients diagnosed with metachronous lesions, the Breslow mean tumor thickness for the first invasive melanoma was 2.27 mm compared with 0.90 mm for the second melanoma. The first melanomas diagnosed are thicker by an average of 3.8 mm (p = 0.008). The mean Clark level for the initial melanoma was greater than the mean level for subsequently diagnosed melanomas (p = 0.002). Twenty-three percent of the initial melanomas were ulcerated, whereas only one of the second primary lesions showed this adverse prognostic factor (p = 0.002). CONCLUSIONS: Once individuals are diagnosed with melanoma, they are in a high-risk population for having other primary site melanomas diagnosed and should be placed in an intensive follow-up protocol consisting of a complete skin examination.

Adult↗
PubMed1997

Intralesional bleomycin-mediated electrochemotherapy in 20 patients with basal cell carcinoma.

BACKGROUND: A new anticancer therapy, electrochemotherapy (ECT), has been introduced that entails exposing cancerous tissues to short pulses of electricity during chemotherapy. This enhances cell membrane permeability and has been shown to have potent antitumor effects in vitro in animal models and in several clinical trials, including nevoid basal cell carcinoma (BCC). OBJECTIVE: We report the effects of ECT on 20 patients with primary BCC. METHODS: Electrical pulses were delivered to 54 tumors after administration of intralesional bleomycin sulfate. RESULTS: Complete responses were observed in 53 (98%), and in the majority of these (94%) after a single treatment. No recurrences have been recorded with a mean of 18 months of observation. CONCLUSION: Although these are preliminary results, ECT appears to be an effective alternative to surgical excision for the treatment of primary BCC.

Adult↗
PubMed1997

The use of selective lymphadenectomy in squamous cell carcinoma of the wrist: a case report.

Squamous cell carcinoma is the second most common skin cancer in humans and has a rate of metastasis of 0.5%-5.9%. Regional lymphadenectomy is generally not recommended for patients with advanced lesions and clinically node-negative disease. Selective lymphadenectomy using preoperative lymphoscintigraphy and intraoperative radiolymphoscintigraphy and vital dye injections to identify the sentinel lymph node may help in staging patients with upper-extremity squamous cell carcinoma while avoiding the complications of a complete axillary node dissection. The case of a patient with a large squamous cell carcinoma of the wrist with clinically negative findings on axillary examination who was found to have a sentinel lymph node containing metastatic tumor is presented. Although this treatment method is still considered investigational, it holds great promise for nodal staging by being able to detect occult metastatic nodal disease in otherwise clinically node-negative patients.

Aged↗
PubMed1997

Sentinel node excision for the diagnosis of metastatic neuroendocrine carcinoma of the skin: a case report.

The technology of sentinel node lymphoscintigraphy has made it possible to map and identify the lymph nodes draining the site of a primary cutaneous malignancy. This technique is now being used in the treatment of melanoma, and breast and vulvar carcinoma. With melanoma and breast carcinoma, the histology of the sentinel lymph node (SLN) has been found to be reflective of the histology of the remainder of the nodal basin. The concept of sampling the SLN is to provide an accurate staging for the entire nodal basin, obviating the need for a complete lymphadenectomy if the SLN is negative. It is believed that cutaneous malignancies with a propensity for regional metastasis, such as neuroendocrine carcinoma of the skin, may spread via a similar lymphatic pathway involving an SLN. Using this technique we identified and excised the SLNs in a patient with a neuroendocrine carcinoma of the skin that contained the only focus of metastatic disease. Although this technique is still investigational we believe it holds great promise in being able to detect occult metastatic nodal disease in clinically node-negative patients.

Aged↗
PubMed1997

Sentinel lymph node biopsy in melanoma of the head and neck.

BACKGROUND: The sentinel lymph node is the first node or nodes to drain a cutaneous melanoma. Sentinel lymph node biopsy is performed to determine whether regional metastases are present. The authors' experience with the new technique of sentinel lymph node biopsy for melanoma of the head and neck is reported. PATIENTS AND METHODS: During the period of January of 1992 to December of 1995, 58 consecutive patients were identified from the melanoma database who had localization of the sentinel lymph node for primary cutaneous melanoma of the head and neck. Techniques for identification of the sentinel node(s) include preoperative lymphoscintigraphy and intraoperative Lymphazurin dye (vital blue dye) and technetium-99m-labeled sulfur colloid injection around the primary tumor site with Neoprobe mapping. RESULTS: Fifty-eight patients (13 female, 45 male), mean age 61 years, with melanoma of the head and neck with a mean Breslow thickness of 2.21 mm. (range, 0.82-6.87 mm.) and no regional lymphadenopathy underwent sentinel node mapping. The sentinel node was successfully identified in 55 patients (95 percent). Blue dye was visualized in 85 of 126 sentinel nodes excised (67 percent), whereas the remainder of the sentinel nodes were localized with the Neoprobe. Forty-nine patients who had successful mapping and sentinel node biopsy had no evidence of metastatic disease in the sentinel node or other nodes in the basin. Six of the fifty-five patients (11 percent) had evidence of micrometastatic disease, and all six had the sentinel node as the only site of metastasis. Five of six patients with micrometastases had a subsequent neck dissection and/or superficial parotidectomy. None of these patients had evidence of "skip metastases" with a negative sentinel node and higher level nodes positive for metastases. In total, 6 of the 18 sentinel nodes (33 percent) identified in these six patients contained micrometastatic disease, whereas none of the 139 other nodes sampled had any evidence of metastases. The exact probability that all six unpaired observations would consist of involvement of only the sentinel nodes is p = 0.0312. CONCLUSIONS: By combining the two mapping techniques in patients with melanoma of the head and neck, the sentinel node(s) can be mapped and identified individually, similar to melanoma in other locations. The sentinel nodes have been shown to contain the first evidence of regional metastatic melanoma. This staging information can be used to plan therapeutic node dissections and adjuvant therapy that may have a survival benefit in patients with stage III melanoma of the head and neck. Lymphatic mapping can be used to make the surgical care of the melanoma patient more conservative, so that only those patients with solid evidence of regional node metastases are subjected to the morbidity and expense of a complete node dissection and the toxicities of adjuvant therapy.

Biopsy↗
PubMed1997

Detection of occult melanoma cells in sentinel lymph nodes and blood.

The presence or absence of regional nodal metastases is the most important prognostic factor for predicting survival in patients with clinical stage I or II cutaneous melanoma. Successful treatment of melanoma patients with primary tumors greater than 0.76-mm thick without clinically palpable nodes is thus critically dependent on identification and biopsy of the sentinel lymph nodes and the detection of possible occult micrometastases in those nodes. Biopsy of sentinel lymph nodes has been greatly facilitated by the development of lymphoscintigraphy. Immunohistochemical and polymerase chainreaction (PCR)-based detection of unique melanoma markers have also dramatically improved our ability to detect nodal micrometastases and assess the risk of recurrence in this patient population. These techniques now make it possible to perform complete lymph node dissection only in those patients with confirmed nodal metastases. The detection of occult melanoma cells in blood using a sensitive multimarker PCR assay is also contributing to the proper staging of melanoma. These techniques have greatly enhanced the oncologist's ability to make rational treatment decisions.

Biomarkers, Tumor↗
PubMed1997

The clinical relevance of sentinel lymph nodes identified with radiolymphoscintigraphy.

BACKGROUND: The purpose of this case report is to illustrate the utility of radio-guided mapping of sentinel lymph nodes (SLN's) as demonstrated by the technique's successful identification of nodes containing metastatic disease that would have been left behind if only the visual-oriented vital blue dye mapping technique had been used. METHOD: The patient underwent preoperative lymphoscintigraphy and intra-operative lymphatic mapping using vital blue dye and radiolymphoscintigraphy using the Neoprobe (handheld gamma probe). Nodes which were blue and/or "hot" (i.e., radioactive counts were three times the background count) were considered SLN's. RESULTS: Four SLN's were harvested, all of which were "hot" but only one of which was both "hot" and blue. Pathology revealed that the two SLN's positive for metastatic disease were not blue. CONCLUSION: While the blue dye lymphatic mapping technique provides the surgeon with a visual road map in the identification of SLN's, the Neoprobe increases the success rate of localization when compared to vital blue dye mapping due to the reliable migration of radiocolloid to the SLN's in the regional basin. Radiolymphoscintigraphy also increases the accuracy and efficiency of the SLN harvest by providing a directed dissection to the level of the nodes in the basin. The Neoprobe increases the yield of SLN's, some of which are clinically relevant since they contain metastatic disease.

Coloring Agents↗
PubMed1996

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer.

OBJECTIVES: To identify the sentinel lymph node(s) (SLN[s]) (the first node[s] draining the primary tumor in the regional lymphatic basin) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla. DESIGN: A prospective trial. PARTICIPANTS: Sixty-two patients with newly diagnosed invasive breast cancers. INTERVENTION: Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid. The SLN was identified and removed, followed by a definitive cancer operation, including a complete axillary node dissection. MAIN OUTCOME MEASURE: The metastatic distribution in the axilla was determined in patients with occult nodal disease. RESULTS: The SLN was successfully identified in 57 (92%) of 62 patients using the 2 lymphatic mapping procedures. After localization, 18 patients (32%) were found to have metastatic disease, and the SLN tested positive in all 18 patients. There were no "skip" metastases, defined as an SLN that tested negative with higher nodes that tested positive. In 12 (67%) of 18 patients with metastatic disease, the SLN was the only site of disease. The metastatic distribution significantly favored SLN involvement. Among subjects with discordant nodal involvement, the probability of observing the distribution of SLN involvement by chance is very small (P<.001). CONCLUSIONS: This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes. The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes, potentially increasing the yield of positive dissections and the accuracy of staging.

Axilla↗
PubMed1996

Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy.

BACKGROUND: Electroporation is a process that causes a transient increase in the permeability of cell membranes. It can be used to increase the intracellular concentration of chemotherapeutic agents in tumor cells (electrochemotherapy; ECT). A clinical study was initiated to determine if this mode of treatment would be effective against certain primary and metastatic cutaneous malignancies. A group of six patients, three with malignant melanoma, two with basal cell carcinoma, and one with metastatic adenocarcinoma, were enrolled in the study. the treatment was administered in a two-step process. METHODS: Each patient received a 10 unit/m2 dose of bleomycin administered intravenously at 1 to 1.5 units/minute. This was followed by eight 99 microsecond pulses at an amplitude of 1.3 kV/cm administered directly to the tumors 5 to 15 minutes after the bleomycin was completely infused. Pulses were administered after the injection of 1% lidocaine solution around the treatment site. RESULTS: Two of three melanoma patients had objective responses. In these two patients, five of six treated tumors decreased in size, and three completely responded. Untreated tumors displayed continued growth. Objective responses were observed in both basal cell carcinoma (BCC) patients. One patient had partial responses in both treated tumors. The other patient had one of four primary BCCs respond completely, and the remaining three respond partially. Patients with metastatic breast adenocarcinoma showed complete responses in both treated nodules after ECT. All patients tolerated the treatment well with no residual effects from the electric pulses. CONCLUSIONS: ECT was an effective local treatment in the majority of nodules treated. The results thus far are very encouraging and the study is being continued.

Adenocarcinoma↗
PubMed1996

Breast cancer patients' personality style, age, and treatment decision making.

BACKGROUND: Previous studies have shown that whereas nearly all cancer patients want information, far fewer wish to make treatment decisions. Although breast cancer patients who were given a choice of lumpectomy versus mastectomy and were encouraged to make the decision were believed to do better psychologically, a 1994 study refuted this. Some authors suggest that patient personality style is an important consideration in decisional preference. METHODS: Newly diagnosed breast cancer patients (n = 76) were surveyed within 6 months of surgery. They answered seven questions about patient and physician roles in the decision-making process. Additionally, they completed the Miller Behavioral Style Scale (MBSS), which categorizes "monitors," or information seekers, and "blunters," or information avoiders. Chi-square analyses were used to explore the relationship of personality style and age to treatment decision-making preferences. RESULTS: Although 80% of women wanted a role in decision making, 74% wanted their surgeons to make a recommendation and when given, 94% followed the recommended treatment plan. Monitors and blunters were equally likely to want physician recommendations. Younger women, particularly those under age 40, were more likely to want a physician's recommendation. Of those women who had specific fears about their cancer (76%), only half of them revealed such fears to their doctors. CONCLUSIONS: The notion that health care consumers, particularly younger ones, desire an independent choice of treatment was contradicted in this study. Physicians are encouraged to provide information and to probe regarding the fears of breast cancer patients in order to reduce anxiety while recognizing that treatment recommendations are desired by most women.

Adult↗
PubMed1996

Bleomycin-mediated electrochemotherapy of basal cell carcinoma.

BACKGROUND: A new technique, electroporation, enhances the antitumor effects of a variety of chemotherapeutic agents. When used in combination with conventional chemotherapy, the procedure is termed electrochemotherapy. Exposure of cancerous tissues to pulses of electricity during electrochemotherapy appears to increase cell membrane permeability and thus intracellular access to cytotoxic drugs. Electrochemotherapy has been shown to have potent antitumor activity in a variety of in vitro studies, animal tumor models, as well as in clinical trials with squamous cell carcinomas of the head and neck. OBJECTIVE: The purpose of the study was to determine the effects of bleomycin-mediated electrochemotherapy on several basal cell carcinomas (BCCs) in two patients with nevoid BCC syndrome. METHODS: Electrical pulses were delivered to tumor nodules by means of caliper electrodes after systemic doses of bleomycin were administered. Vital signs were closely monitored during application of the electrical pulses. RESULTS: Partial responses were observed in tumors from both of the patients treated with electrochemotherapy; three partial responses were observed in one patient, and one partial response was observed in the other patient. Complete responses were seen in two lesions. Only minimal local or systemic side effects were noted in response to the therapy. CONCLUSION: To our knowledge, this is the first study that documents the effects of bleomycin-mediated electrochemotherapy on BCC. Studies are ongoing with intralesional bleomycin during electrochemotherapy to see whether additional antitumour effects can be produced in patients with BCC by this route of administration.

Adult↗
PubMed1996

Intraoperative radio-lympho-scintigraphy improves sentinel lymph node identification for patients with melanoma.

BACKGROUND: The sentinel lymph node (SLN), the first node draining the primary tumor site, has been shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma. Intraoperative localization of the SLN, first proposed by Morton and colleagues, has been accomplished with the use of a vital blue dye mapping technique. Technical difficulties resulting in unsuccessful explorations have occurred in up to 20% of the dissections. OBJECTIVES: The authors aimed to define the SLN using gamma detection probe mapping and to determine whether intraoperative radiolymphoscintigraphy using technetium sulfur colloid and a hand-held gamma-detecting probe could be used to improve detection of all SLNs for patients with melanoma. METHODS: To ensure that all initial nodes draining the primary site were removed at the time of selective lymphadenectomy, the authors used intraoperative radiolymphoscintigraphy to confirm the location of the SLN, which was determined initially with the preoperative lymphoscintigram and the intraoperative vital blue dye injection. PATIENT POPULATION: The patient population consisted of 106 consecutive patients who presented with cutaneous melanomas larger than 0.75 mm in all primary site locations. RESULTS: The preoperative lymphoscintigram revealed that 22 patients had more than one lymphatic basin sampled. Two hundred SLNs and 142 neighboring non-SLNs were harvested from 129 basins in 106 patients. After the skin incision was made, the mean ratio of hot spot to background activity was 8.5:1. The mean ratio of ex vivo SLN-to-non-SLN activity for 72 patients who had SLNs harvested was 135.6:1. When correlated with the vital blue dye mapping, 139 of 200 (69.5%) SLNs demonstrated blue dye staining, whereas 167 of 200 (83.5%) SLNs were hot according to radioisotope localization. With the use of both intraoperative mapping techniques, identification of the SLN was possible for 124 of the 129 (96%) basins sampled. Micrometastases were identified in SLNs of 16 of the 106 (15%) patients by routine histologic analysis. CONCLUSION: The use of intraoperative radiolymphoscintigraphy can improve the identification of all SLNs during selective lymphadenectomy.

Adolescent↗
PubMed1996

Bleomycin-mediated electrochemotherapy of metastatic melanoma.

BACKGROUND: Electroporation is a new technique that enhances the antitumor effects of chemotherapy by exposing cancerous tissues to pulses of electricity. When used in combination with conventional chemotherapy, the procedure is termed electrochemotherapy (ECT). The electric pulses increase cell membrane permeability and thus intracellular access. Electrochemotherapy has been shown to have potent antitumor activity in a number of in vitro studies, several animal models, and clinical trials with squamous cell carcinomas and basal cell carcinomas. OBJECTIVE: To report the effects of ECT in 5 patients with metastatic malignant melanoma. RESULTS: Twenty-three lesions of metastatic melanoma were treated with intralesional bleomycin sulfate followed by pulses of electricity. Pulses were delivered via caliper or needle electrodes placed around the tumor. Complete responses were observed in 18 tumors (78%) and partial responses were seen in 4 (17%). No responses were seen in lesions treated with either pulses or bleomycin alone. Vital signs were closely monitored during the procedure, and minimal side effects were noted. CONCLUSIONS: This is the first study that documents the antitumor effects of ECT in metastatic melanoma. Although not a cure, it may be an effective alternative to palliative surgery or irradiation in these patients.

Adult↗
PubMed1995

Interleukin 15 induction of lymphokine-activated killer cell function against autologous tumor cells in melanoma patient lymphocytes by a CD18-dependent, perforin-related mechanism.

Interleukin 15 (IL-15) is a novel cytokine that shares no homology with IL-2, but it requires the use of beta and gamma chains of the IL-2 receptor complex for binding and signaling. In vitro studies have shown induction of CTL and lymphokine-activated killer (LAK) cell activity in peripheral blood mononuclear cells (PBMCs) from normal donors by IL-15 against known tumor targets. The present study attempts to define the role of IL-15 in generating LAK activity from melanoma patient lymphocytes. PBMCs of patients newly diagnosed with metastatic melanoma were incubated with different doses of recombinant human IL-15 and tested against autologous tumor cells, LAK sensitive cell lines (i.e., FMEX and Daudi), as well as the natural killer-sensitive cell line K562, in a 15-h 51Cr release assay. The effect of IL-15 was found to be both time and dose dependent, with peak activity detected after 2 or 3 days of culture with 100 ng/ml of this cytokine. LAK and not CTL activity in patient PBMCs was detected by the inability of mAbs against CD4, CD8, and MHC class I to effectively block lysis of autologous tumor and FMEX melanoma cells. In addition, interaction via the CD18 adhesion molecule was shown to be critical in IL-15-induced LAK-mediated lysis of autologous tumor cells. Finally, incubation of patient PBMCs with IL-15 for 6 h resulted in the up-regulation of perforin mRNA transcription. These findings suggest that LAK activity can be generated from melanoma patient PBMCs in the presence of IL-15 to lyse autologous tumor cells in a non-MHC-restricted manner. This new cytokine may play an important role in antitumor immunity with a possible use for cancer immunotherapy.

Biopsy↗