Clinical Lymphadenopathy Research Articles

Anti-CCR7 monoclonal antibodies as a novel tool for the treatment of chronic lymphocyte leukemia

To date, chronic lymphocytic leukemia (CLL) remains incurable with current treatments, which include the monoclonal antibodies (mAbs) rituximab and alemtuzumab. The efficacy of rituximab is modest when used as single agent, and alemtuzumab induces severe immunosuppression. To develop more potent and specific therapies, we propose the CC chemokine receptor 7 (CCR7) as an attractive target molecule to treat CLL, as it not only fulfills the requirements of a high-surface expression and a good level of tissue specificity, but it also plays a crucial role in mediating the migration of the tumor cells to lymph nodes (LNs) and thus, in the development of clinical lymphadenopathy. In the current work, murine anti-human CCR7 mAb mediated a potent, complement-dependent cytotoxicity (CDC) against CLL cells while sparing normal T lymphocytes from the same patients. The sensitivity to CDC was related to the antigenic density of CCR7. Moreover, these mAb blocked the in vitro migration of CLL cells in response to CC chemokine ligand 19 (CCL19), one of the physiological ligands of CCR7. Conversely, CLL cells were poorly lysed through antibody-dependent, cell-mediated cytotoxicity (ADCC), probably as a result of the murine origin and the isotype of the anti-CCR7 mAb used. Molecular engineering techniques will allow us to obtain chimeric or humanized anti-CCR7 mAb to reach the best clinical response for this common and yet incurable leukemia.

Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination.

B cell neoplasms present heterogeneous patterns of lymphoid organ involvement, which may be a result of the differential expression of chemokine receptors. We found that chemokine receptor (CCR)7, CXC chemokine receptor (CXCR)4, or CXCR5, the main chemokine receptors that mediate B cell entry into secondary lymphoid tissues and their homing to T cell and B cell zones therein, were highly expressed in B malignancies with widespread involvement of lymph nodes. Conversely, those pathologies with little or no nodular dissemination showed no expression to very low levels of CCR7 and CXCR5 and low to moderate levels of CXCR4. These findings provide evidence for the role of CCR7, CXCR4, and CXCR5 in determining the pattern of lymphoid organ involvement of B tumors. Functional studies were performed on B malignancies expressing different levels of CCR7, CXCR5, and CXCR4. Multiple myeloma (MM) cells did not express CCR7 nor CXCR5 and did not migrate in response to their ligands; a moderate expression of CXCR4 on MM cells was accompanied by a migratory response to its ligand, CXCL12. By contrast, cells from B cell chronic lymphocytic leukemia (B-CLL) expressed the highest levels of these chemokine receptors and efficiently migrated in response to all ligands of CCR7, CXCR4, and CXCR5. In addition, the migration index of B-CLL cells in response to both of the CCR7 ligands correlated with the presence of clinical lymphadenopathy, thus indicating that the high expression of functional chemokine receptors justifies the widespread character of B-CLL, representing a clinical target for the control of tumor cell dissemination.

The chemokine receptor CCR7 and α4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes

AbstractMalignant lymphocyte migration into lymph nodes is an important aspect of chronic lymphocytic leukemia (CLL), yet little is known about the processes involved. Here we demonstrate that CLL cells migrate across vascular endothelium in response to at least 3 chemokines, namely, CCL21, CCL19, and CXCL12. Moreover, transendothelial cell migration (TEM) in response to CCL21 and CCL19 was significantly higher for the malignant B cells of patients who had clinical lymph node involvement as compared with those of patients lacking such organomegaly. Furthermore, the expression of CCR7, the receptor for both CCL21 and CCL19, correlated with clinical lymphadenopathy, and blocking of CCR7 inhibited CLL cell TEM. By using immunohistochemistry we demonstrated that CCL21 and CCL19, but not CXCL12, are located in high endothelial venules and are, therefore, in an appropriate location to induce TEM. Regarding the adhesion receptors involved in TEM, α4 (most likely in association with β1) and αLβ2 were shown to be important in CLL cell TEM in vitro, but only the level of α4 expression correlated with the presence of clinical lymphadenopathy. The present studies are the first to shed light on the factors determining CLL cell entry into nodes and define the phenotype of circulating malignant cells likely to determine the pattern of lymph node enlargement in the disease.

Risk of bilateral cervical lymph node metastases in papillary thyroid cancer

We evaluated the risk of bilateral or contralateral cervical lymph node metastases in 135 patients with papillary thyroid cancer who underwent bilateral neck dissection. We confirmed that bilateral jugular lymph node metastases were frequent in patients with obvious carcinoma in both lobes of the gland, in those with cancers arising in the isthmus, in those with clinically detectable bilateral lymphadenopathy, and in those with recurrent thyroid cancer. However, only 24% of the patients who had cancer clinically confined to one lobe with no bilateral or contralateral lymphadenopathy had histologically detected bilateral or contralateral jugular lymph node metastases. But the occurrence of contralateral jugular lymph node metastases was significantly correlated with both clinical lymphadenopathy in the ipsilateral neck and contralateral paratracheal lymph node metastases. Bilateral lymph dissection might be beneficial for these patients.

Dermatopathic lymphadenopathy and lymph node involvement in mycosis fungoides.

Lymph node involvement in mycosis fungoides (MF) is associated with a poor prognosis, Histologically, in most cases of clinical lymphadenopathy the excised lymph node shows dermatopathic lymphadenopathy (DL). The diagnosis of MF involvement can readily be made when the lymph node tissue has partly or wholly been replaced by atypical lymphoreticular tissue. Early involvement of a dermatopathic lymph node by MF may be difficult to diagnose. A histologic study was performed on 30 lymph nodes from 24 patients with MF. Most of these lymph nodes had been excised as part of the staging procedure. The maximal follow-up period was five years. A classification of lymph node involvement into four categories is suggested and correlations with clinical courses and results of DNA cytophotometry of lymph node imprints are shown. Lymph nodes showing the histologic picture of DL can be divided into two groups: a group with MF involvement (category I) and a group with MF involvement (category II). The latter group is considered to represent early involvement of lymph nodes by MF. Partial or complete replacement of lymph node tissue by atypical lymphoreticular tissue corresponds with cagegories III and IV, respectively.

Clinicopathological Study of Oral Cancer*

SummaryPresent study is based on the observations of 25 cases of oral cancer. Males are affected more commonly in S5th and 6ih decade. Clinical lymphadenopathy in the neck is observed in 84% of cases which was confirmed on hisiology in only 56% cases. Clinically the disease is more advanced than its histological grade. Inflammatory infiltrate in the primary tumour and germinal centre hyperplasia, paracortical activity and sinus histiocytosis in the Iymphnodes are suggestive of immunological response against the tumour whereas capsular and pericapsular invasion of lymph nodes are suggestive of poor prognosis.

THE MANAGEMENT OF CERVICAL LYMPH NODE METASTASIS BY MEGAVOLTAGE RADIOTHERAPY

THE MANAGEMENT OF CERVICAL LYMPH NODE METASTASIS BY MEGAVOLTAGE RADIOTHERAPYG. E. HANKS, M.D., M. A. BAGSHAW, M.D. and H. S. KAPLAN, M.D.Audio Available | Share