Transimmunization: the science catches up to the clinical success.
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Humans↗
Biomedical subjects
R L Edelson
Publications and source records attributed to R L Edelson.
Induction of human tumor-loaded dendritic cells.
A preferred anti-cancer vaccine would be tumor-specific, simple to rapidly construct and safe to administer. It would permit immunization against a spectrum of the tumor's distinctive antigens, without requiring their prior identification. Toward these goals, we describe a modification of standard extracorporeal photopheresis (ECP) which initiates, within a single day, both monocyte-to-dendritic cell (DC) differentiation and malignant cell apoptosis. The transition of monocytes to immature DCs was identified by the expression of cytoplasmic CD83 and membrane CD36 in the absence of membrane CD14 staining, as well as induction of membrane CD83 expression. Differentiating DCs were avidly phagocytic and engulfed apoptotic malignant T cells. Differentiating DCs were capable of stimulating significant proliferation of normal alloreactive lymphocyte responders, indicting increased expression of membrane MHC class II molecules. This approach provides a clinically practical means of developing tumor-loaded cells that have initiated the transition to DCs without the requirement of exogenous cytokines, excessive cellular manipulation or isolation. Construction of DC vaccines using this methodology can be generalized to other diseases and may offer a novel approach for improved cancer immunotherapy.
Antigens, CD↗
Cutaneous T cell lymphoma: the helping hand of dendritic cells.
Since its introduction 25 years ago, cutaneous T cell lymphoma has become the preferred designation for clonal malignancies of those CD4 thymus-derived lymphocytes ("cutaneous T cells") that preferentially migrate to skin. The varied cutaneous clinical presentations, dependent on the specific features of the dominant subclones of the malignant lymphocytes, historically led to confusing descriptive terms (mycosis fungoides, Sézary syndrome, lymphoma cutis, leukemia cutis, reticulum cell sarcoma of the skin). Recognition that all of these clinical presentations are cancers of a single type of cell has permitted their unification under the single, clarified heading cutaneous T cell lymphoma, or CTCL. As a neoplastic amplification of the skin-homing T cells from which it is derived, CTCL's distinctive features can be explained. The triad of skin localization, remarkable avoidance of bone marrow, often even in the context of extremely high leukemic counts, and infiltration of perifollicular T cell zones of the lymph nodes and spleen reflect the migratory pathway and homing patterns of cutaneous T cells. The usually retained levels of serum immunoglobulins and the resulting capacity to defend against encapsulated bacteria, often even in advanced CTCL, are manifestations of the helper function of the malignant T cells-that is, their functional capacity to stimulate B lymphocytes to produce immunoglobulin in a polyclonal manner. In contrast, the often-extreme normal T cell deficits in advanced CTCL, equivalent to those of late-stage AIDS, probably resulting from the production of suppressive cytokines such as IL-10, cause susceptibility to a broad range of opportunistic infections, the most common direct cause of death. Pautrier microabscesses, the pathognomonic feature of epidermotropic early CTCL, hold the clues to the pathogenesis of the cancer. These intraepidermal collections of stimulated and proliferating malignant cells, adherent to the dendrites of intraepidermal dendritic antigen-presenting cells (Langerhans' cells [LCs]), indicate a dynamic communication between the two cell types. Since CTCL cells are derived from CD4 T cells, which normally receive signaling from dendritic cells (DCs) via presentation of antigenic peptides as part of class II major histocompatibility complexes to antigen-specific T cell receptors (TCRs), it seems likely that CTCL is a clonal proliferation of T cells responding to specific antigenic stimulation from LCs. This is supported by our recent finding that CTCL cells proliferate in vitro in response to TCR stimulation by autologous DCs, which have previously ingested and processed antigens from apoptotic autologous CTCL cells. In short, CTCL may be a malignancy of T cells stimulated to proliferate against its own tumor antigens. The most intriguing possibility is that a yet-unidentified transforming retrovirus, harbored by LCs, simultaneously attracts, stimulates, and transforms a single clone of antigen-specific cutaneous T cells. Longstanding disease-free remissions have been induced by transimmunization (via a photopheresis apparatus). This treatment, introduced more than a decade ago by our group and the first and still the only FDA-approved selective anticancer immunotherapy, has been performed more than 200,000 times worldwide on advanced CTCL, as well as in reversal/prevention of heart transplant rejection and treatment of graft-versus-host disease and selected autoimmune disorders. Transimmunization induces clinically relevant suppression, and occasionally elimination, of pathogenic T cell clones. The common denominator between these diverse groups of responding patients is the presence of clonally distinctive TCRs on the disease-causing malignant or autoaggressive T cell clones. In CTCL at least one source of tumor-specific antigens is derived from the clone-specific (idiotypic) segments of the TCR protein chains. In the photopheresis apparatus, two synergistic phenomena are initiated: induction of apoptosis of the CTCL cells and mass conversion of blood monocytes to DCs. The young DCs then ingest the apoptotic CTCL cells, process and present the CTCL antigens to responding anti-CTCL cytotoxic T cells, and stimulate clinically important CTCL suppression. Now that it is better understood, transimmunization may have much broader applications in other types of cancer as well.
Antigen Presentation↗
Pemphigus--decoding the cellular language of cutaneous autoimmunity.
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Autoantibodies↗
Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides.
OBJECTIVE: We compared the prognosis of patients with erythrodermic mycosis fungoides (MF) administered total skin electron beam radiation (TSEB) plus neoadjuvant, concurrent, and adjuvant extracorporeal photopheresis (ECP) with the prognosis of patients administered only TSEB. Outcomes of clinical interest include disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and cause-specific survival (CSS). METHODS: This study was a retrospective nonrandomized series. Between 1974 and 1997, a total of 44 patients with erythrodermic MF from the Department of Therapeutic Radiology, Yale University School of Medicine, and the Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Ontario, were collected and analyzed as a group (Hamilton = 15, Yale = 29). These patients received TSEB consisting of 32 to 40 Gy via 4 to 6 MeV. Twenty-one patients at Yale also received ECP treatment 2 days per month for a median of 6 months. Median age was 68 years (range, 29-82 years) at the commencement of TSEB, and 66% were male. Seventy-three percent of patients had received other therapies before TSEB, including 75 courses that failed to control disease (n = 15 systemic therapy, 16 biologicals, and 44 topical therapies). At TSEB, 59% had hematologic involvement (B1), 30% were stage IVA (N3), and 13% were IVB (M1). Median follow-up was 2.2 years (range, 0.3-13.9 years) subsequent to TSEB and 3.7 years from diagnosis (range, 0.8-16.8 years). RESULTS: All patients responded to TSEB within 2 months of completion, with a cutaneous complete response rate of 73%. For the 32 complete responders the 3-year DFS was 63%. It was 49% for those 17 patients who received only TSEB compared with 81% for those 15 patients who received TSEB + ECP. Cox regression analysis demonstrated that ECP was associated with prolonged remission (DFS multivariate P =.024, adjusting for B1 and stage). The 2-year PFS, CSS, and OS for the TSEB group were 36%, 69%, and 63%, respectively, compared with 66%, 100%, and 88% for the TSEB + ECP cohort. Cox regression demonstrated that ECP was associated with CSS (multivariate P =.048, adjusting for B1 and stage). For those who progressed, a total of 49 subsequent courses of therapy were administered (n = 20 chemotherapy, 10 biologicals, and 19 topical therapies). Thirteen patients died from MF-related causes, and 8 died from other causes. Acute and chronic toxicities were consistent with those previously reported. CONCLUSION: ECP given concurrently with, or immediately after, TSEB (32-40 Gy) significantly improves both PFS and CSS for patients with erythrodermic MF compared with TSEB without the addition of ECP.
Adult↗
P-glycoprotein expression and multidrug resistance in cutaneous T-cell lymphoma.
Advanced-stage cutaneous T-cell lymphoma (CTCL) is generally resistant to standard chemotherapy. Because P-glycoprotein (P-gp) has been detected in other types of resistant solid tumors, leukemias, and lymphomas, we analyzed P-gp expression in CTCL. Twenty-seven patients with CTCL and circulating Sezary cells in the peripheral blood as observed on a peripheral smear treated at the Yale Photopheresis Center between 1987 and 1993 were identified. Twenty-five of these patients had skin biopsies evaluated for expression of P-gp using JSB-1 (Accurate Chemical), MRK-16 (gift of T. Tsuruo), and UIC-2 (gift of E. Metchner). P-gp expression was considered present if immunoreactivity was noted with two of the three antibodies. Eighteen of 25 patients (72%) evaluated exhibited expression. The patients were treated with various combinations of drugs consisting of topical and systemic steroids electron beam therapy, psoralens in combination with UV light A (PUVA), systemic chemotherapy, and photopheresis before testing the tissue for P-gp expression. Treatment with systemic chemotherapy in P-gp-positive patients produced responses in 3 and no responses in 11 patients (4 were lost to follow-up). Seven patients did not express P-gp: One patient responded to treatment, five did not respond, and one patient was lost to follow-up. These results demonstrate that P-gp is frequently expressed in CTCL. P-gp expression in our study was not a useful predictor of drug resistance.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Cutaneous T-cell lymphoma: pathogenesis and treatment.
Cutaneous T-cell lymphoma (CTCL) is a malignancy of a distinctive subset of T-helper cells designated "cutaneous T cells" because of their central role in the normal functioning of the skin immune system. Guided by selective adhesion molecules, activated/memory T cells of the skin immune system normally circulate among the skin, lymph nodes, and peripheral blood. Thus, a better understanding of the skin immune system, which normally functions to provide immunosurveillance against cutaneous pathogens and other insults, has led to a better understanding of the clinical spectrum, pathogenesis, staging, and management of CTCL. This article describes the major subtypes of CTCL and provides an update on the pathogenesis and treatment of this lymphoma.
Forecasting↗
Sézary syndrome, cutaneous T-cell lymphoma, and extracorporeal photopheresis.
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Humans↗
Integrins alpha4beta7 and alphaEbeta7 are expressed on epidermotropic T cells in cutaneous T cell lymphoma and spongiotic dermatitis.
Integrin alpha4beta7 has been associated with tissue-specific homing of malignant and inflammatory lymphocytes to gastrointestinal mucosa, whereas integrin alphaEbeta7 has been associated with intraepithelial lymphocytes in both the gut and the skin. This prompted us to examine the expression of alpha4beta7 on skin-infiltrating lymphocytes in 12 cases of patch/plaque stage cutaneous T cell lymphoma (CTCL) and in 4 cases of spongiotic dermatitis, which also display intraepidermal T cell accumulation. alpha4beta7 was found to be expressed on 64.8+/-7.4% of intraepidermal and 39.1+/-5.0% of intradermal T lymphocytes in CTCL. There was a significant positive correlation (r=0.58) between the degree of epidermotropism and the percentage of intraepidermal T cells expressing alpha4beta7. Similar findings were observed in spongiotic dermatitis, indicating that this result is not unique to malignant T cells. We evaluated staining of T cells in the same specimens for presence of alphaEbeta7 and observed a strong correlation between the expression of both beta7 integrins in each specimen. Staining with antibodies directed against the known ligands of alpha4beta7 was also performed on skin biopsies from CTCL patients. There was significantly increased dermal microvascular endothelial expression of vascular cell adhesion molecule-1 in lesional compared with nonlesional skin, and in nonlesional skin compared with skin of normal control subjects. Dermal and epidermal expression of the CS-1 domain of fibronectin was present but not increased in lesional biopsies compared with nonlesional or normal controls, whereas expression of mucosal addressin cell adhesion molecule-1 was not detectable in any skin biopsy specimens. In summary, alpha4beta7, like alphaEbeta7, is expressed at high levels on epidermotropic T cells and may interact with endothelial cell vascular cell adhesion molecule-1 as part of stepwise recruitment of lymphocytes from the blood to the epidermis.
Biopsy↗
Photoactivated 8-methoxypsoralen treatment causes a peptide-dependent increase in antigen display by transformed lymphocytes.
Ex vivo exposure of malignant human T cells to photoactivated 8-methoxypsoralen (8-MOPa), followed by their i.v. return, appears to vaccinate patients against tumor-associated antigens of cutaneous T cell lymphoma in a procedure termed photopheresis. The molecular basis of this Food and Drug Administration-approved therapy, administered in 100 centers worldwide, is unclear. Most of the attention to the mechanism of action of the drug has focused on its capacity to form covalent cross-links with pyrimidine bases of DNA, thereby inhibiting cellular proliferation. Because immunologic factors appear to be important in the clinical response and could potentially serve as a model for immunotherapy of other malignancies, we explored the possibility that 8-MOP-treated cells display increased quantities of antigenic peptides at their cell surface. In this work, human B-lymphoblastoid tissue culture lines were exposed to 8-MOPa and expression of cell surface class I major histocompatibility complex proteins assessed, since CD8 T cells recognize antigenic moieties in the context of class I molecules. A peak 200-300% increase in MHC class I expression in 8-MOPa-treated cells occurred at 20 hr. 8-MOPa was far more effective in inducing this increase in class I MHC than other modalities, including mitomycin C, gamma-irradiation, ultraviolet B or heat or cold shock. This increase in surface class I MHC molecules appears to be driven by the degradation of cytoplasmic proteins into small peptides, followed by the transport of these peptides to MHC class I molecules in the endoplasmic reticulum. The data suggest that 8-MOPa treatment may augment the immunogenicity of tumor and/or antigen-presenting cells by enhancing processing and transport of class I MHC antigenic peptides.
B-Lymphocytes↗
Tumor-specific peptides in cutaneous T-cell lymphoma: association with class I major histocompatibility complex and possible derivation from the clonotypic T-cell receptor.
We wished to identify and characterize tumor-associated class I peptides which could potentially serve as immunogens for an immunoprotective CD8 response in cutaneous T-cell lymphoma (CTCL). Candidate idiotypic peptides were identified from the third complementarity determining region (CDR3) of the clonotypic T-cell receptor (TCR) expressed on malignant T cells and native class I peptides were identified from CTCL cells. Idiotypic peptides were designed by sequencing of patients' CDR3 and identifying 9 amino acid peptides that could be accommodated in the peptide-binding motif of the class I alleles. Three candidate idiotypic peptides were synthesized and tested by measuring release of tumor necrosis factor-alpha (TNF-alpha) from autologous CD8 cells. Native peptides were acid-eluted from class I molecules on CTCL lymphocytes, fractionated, tested in the TNF-alpha assay and sequenced. Two unique idiotypic peptides were specifically recognized by autologous CD8 cells from CTCL patients. In addition, a native peptide eluted from class I molecules of CTCL tumor cells was identified, in the protein data base, as a novel molecule with partial sequence homology to the conserved portion of the patient's TCR. This homology was used to construct an extended native peptide sequence that was immunogenic for CD8 cells from both CTCL patients. Our results demonstrate that peptides derived from the TCR can be used as tumor-specific immunogens that are recognized by CD8 cells. Moreover, novel class I peptides isolated from the tumor cell also serve as immunogens. These peptides might form the basis of an anti-tumor vaccine for immunotherapy of CTCL.
Amino Acid Sequence↗
Spread of antibiotic-resistant bacteria from acne patients to personal contacts--a problem beyond the skin?
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Acne Vulgaris↗
Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides).
PURPOSE: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND MATERIALS: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). RESULTS: Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1 receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01). For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA therapy was acceptable, with only two patients requiring a reduction in PUVA dosage. CONCLUSION: PUVA can maintain remissions in patients with CTCL after TSEBT. There is a significant benefit in DFS but no statistically significant improvement in OS. Prospective, randomized data are needed to confirm these results. PUVA is also effective as a salvage therapy after TSEBT in early-stage patients with recurrence, with acceptable toxicity.
Administration, Oral↗
A lymphocyte cell surface heat shock protein homologous to the endoplasmic reticulum chaperone, immunoglobulin heavy chain binding protein BIP.
BE2 is a cell surface monomeric 78-kDa protein (BE2-78) expressed on the malignant lymphocytes of cutaneous T-cell lymphoma and adult T-cell leukemia, on some lymphocytes from patients with acquired immunodeficiency syndrome and on Epstein-Barr virus-transformed B cells. BE2-78 positivity of cutaneous T-cell lymphoma tumor cells is a useful diagnostic and prognostic determinant in evaluating patients with that disorder. The BE2-78 protein was isolated from Epstein Barr virus-transformed B cells, purified by 1- and 2-dimensional electrophoresis and then sequenced. The sequence of 4 isolated peptide fragments was highly homologous with the 78-kDa heat shock protein, BiP, an endoplasmic reticulum chaperone. The similarity between BiP and BE2-78 was supported by the demonstration that BE2-78, like BiP, avidly binds to ATP. However, polyclonal and monoclonal reagents that recognize cytoplasmic 70- and 78-kDa heat shock proteins do not detect the BE2-78 antigen on the cell surface of cutaneous T-cell lymphoma or Epstein Barr virus-transformed lymphocytes, and peptide mapping demonstrates sequence divergence, suggesting that either they are distinct or conformationally different molecules. Our results indicate that BE2-78 is a cell surface heat shock protein. The possibility that malignant or transformed lymphocytes may express cell surface molecules with the capacity to bind a spectrum of exogenous or endogenous peptides has potential implications for tumor immunology.
Adenosine Triphosphate↗
Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk.
Malignant cells of patients with cutaneous T cell lymphoma (CTCL) are of monoclonal origin and of the CD4+/CD45RO+ subset. Since unlike their normal counterparts, triggering of their TCR/CD3 in vitro elicits only a weak mitogenic response, we set out to determine which of the signal transduction molecules initiated by anti-CD3E antibodies are affected in neoplastic cells. The results obtained from analysis of tumor cells from four patients show a general reduction in basal and induced tyrosine phosphorylation of a wide range of signaling proteins. Furthermore, the function of members from distinct families of protein tyrosine kinases was altered in neoplastic cells. The enzymatic activity of the membrane-bound fraction of Csk was suppressed, and its association with other cellular proteins was altered. There was a decline in the amount and activity of Syk, and a slight decrease in the specific activity of Lck kinases. Zap70 tyrosyl phosphorylation was reduced or undetectable and the kinase associated weakly, or not at all, with the TCR zeta chain. We propose that dampened TCR-triggered responses in CTCL are caused by suppression of an array of effector molecules required for coupling cell surface receptors to early and late signaling events.
Adult↗
Additional courses of total skin electron beam therapy in the treatment of patients with recurrent cutaneous T-cell lymphoma.
BACKGROUND: Recurrent cutaneous T-cell lymphoma (CTCL) is managed with a variety of modalities. Repeat treatment with additional courses of total skin electron beam therapy (TSEBT) has not been formally evaluated. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of additional TSEBT for recurrent CTCL. METHODS: A total of 14 patients were treated with TSEBT and received at least two courses, with five of those patients receiving a third course. Patients were offered additional TSEBT if they suffered recurrence despite other therapy if the extent of the recurrence precluded localized radiation. The median follow-up was 36 months. RESULTS: The median dose for the entire group was 57 Gy. Thirteen patients (93%) achieved a complete response (CR) after the initial course. After the second course, 12 patients (86%) had a CR; of the five patients who underwent a third course, three (60%) achieved a CR. The median disease-free interval after the first course of therapy for those with a CR was 20 months and 11.5 months after the second course. Median survival after the second course was 15 months. All patients had xerosis, pruritus, desquamation, mild erythema, epilation, and anhidrosis of the skin. CONCLUSION: Patients with recurrent CTCL recalcitrant to other forms of therapy or too diffuse for treatment with localized radiation fields are candidates for additional TSEBT. This therapy is effective and well tolerated with an acceptable risk profile.
Adult↗
Induction of functional empty class I major histocompatibility complex glycoproteins by photoactivated 8-methoxypsoralen.
CD8+ cytotoxic T lymphocytes (CTLs) bind to and selectively lyse tumor cells via T-cell receptor recognition of distinctive peptide antigens presented in the context of surface major histocompatibility complex class I (MHC class I) glycoproteins. Several human and experimental animal tumors express distinctive MHC class I-associated peptides, which can be selectively targeted by specific CD8+ CTLs. Malignant cells expressing low quantities of these peptides are poor inducers of CTL responses. Therefore, we have developed a method of externally loading increased amounts of antigenic peptides onto MHC class I molecules. In order to induce "empty" fillable MHC class I molecules capable of binding antigenic peptides, we exposed transformed murine T cells (RMA) to low dose (3 joules/cm2) ultraviolet A energy and 8-methoxypsoralen (100 ng per ml). Presence of "empty" class I molecules was ascertained by "meltdown" or loss of the thermodynamically unstable cold-induced "empty" molecules as identified by cytofluorography at 37 degrees C. Retained function of "empty" molecules was determined by their stabilization through addition of peptides of the correct size and sequence motif, prior to exposure to physiologic temperature.
Animals↗
The immune response to class I-associated tumor-specific cutaneous T-cell lymphoma antigens.
In order to determine whether the neoplastic T cells from patients with cutaneous T-cell lymphoma express tumor-specific antigens that can serve as the targets of an immune response, we took advantage of family-specific monoclonal antibodies, magnetic bead technology, and recombinant cytokines, which provided the previously precluded ability to isolate and expand populations of purified tumor and autologous CD8 cytotoxic T cells. Four patients with advanced cutaneous T-cell lymphoma had CD8 cells that specifically killed autologous tumor in a class I limited fashion. Tumor cell cytolysis could be specifically enhanced by pre-culture with autologous gamma-irradiated tumor. The cytolytic T cells produced tumor necrosis factor-alpha in response to stimulation with autologous tumor. The presence of tumor-specific cytotoxic T cells recognizing distinctive class I associated molecules on cutaneous T-cell lymphoma tumor cells suggests that infiltration of early lesions by CD8 cells reflects host immunity to the neoplasm. These studies provide the foundation for the development of tumor vaccines through the use of cytotoxic T cells to isolate and characterize tumor-associated cutaneous T-cell lymphoma peptides.
Antibody Formation↗