Hypothesis: HOMING OF LYMPHOCYTES TO NON-LYMPHOID TISSUES

doi:10.1016/S0140-6736(74)92597-5

The Lancet

Volume 303, Issue 7852, 23 February 1974, Pages 292-293

https://doi.org/10.1016/S0140-6736(74)92597-5 Get rights and content

Abstract

Two major subpopulations of lymphocytes, thymus dependent (T) and bursa equivalent (B) are now recognised. In spleen, lymph-nodes, and other secondary lymphoid organs these subpopulations occupy separate anatomical compartments' to which circulating T and B lymphocytes "home" appropriately by a process which has been called "ecotaxis". From the behaviour of extranodal lymphoid tumours in man it is suggested that small numbers of circulating lymphocytes may normally home on quite sharply defined areas of the body not usually regarded as secondary lymphoid organs, and that this may help to explain the curious distribution of various pathological lesions characterised by lymphoid infiltration. A similar principle may also apply to "lymphoid" cells other than lymphocytes.

References (19)

J.L. Preud'homme et al.
Blood
(1972)
L. Mårtensson
Lancet
(1963)
J.L. Gowans et al.
Proc. R. Soc. B.
(1964)
A.E. Gabrielsen et al.
B.H. Waksman et al.
J. exp. Med.
(1962)
M.A.B. de Sousa et al.
M. de Sousa
Clin. exp. Immun.
(1971)
P.J. Fialkow
C. Wiseman et al.
Cancer
(1972)

There are more references available in the full text version of this article.

Cited by (41)

Pure abscopal effect of radiotherapy in a salivary gland carcinoma: Case report, literature review, and a search for new approaches
2020, Cancer/Radiotherapie
Citation Excerpt :
They hypothesized that skin—and, by extension, the rest of the body—was a mosaic of clonal cell populations that harbored different susceptibilities to autoimmune insults, which would account for the appearance of isolated (and at times symmetrically distributed) lesions on the skin surface, affecting one specific portion of the skin surface rather than all of it [238]. They intuited that a similar process might explain how and why B and T lymphocytes homed to distinct anatomical compartments [239] and that, if transformed, they might home to some particular body site or set of body sites that expressed some particular epitope corresponding to the receptor expressed by the neoplastic lymphocyte [239,240]. If their intuition was correct, and if the specific epitope could be identified, then it might be possible to block the receptor of the neoplastic lymphocyte or the epitope of the target site and treat the corresponding disease [240].
We report the case of an 84-year-old woman with poorly differentiated non-small cell carcinoma of the right parotid who presented with headache, was found to have a primary right parotid gland cancer as well as metastatic disease, and underwent palliative radiotherapy to the primary site. The patient received no chemotherapy or immunotherapy, but both the primary site and several non-irradiated foci in the lungs regressed or completely resolved. The patient remained free of disease for about one year before progression. The case is a rare instance of abscopal regression of metastatic disease in the absence of pharmacologic immunomodulation. A literature review surveys the history of the abscopal effect of radiation therapy, attempts to understand the mechanisms of its successes and failures, and points to new approaches that can inform and improve the outcomes of radioimmunotherapy.
Nous rapportons ici le cas clinique d’une femme âgée de 84 ans qui s’est présentée avec un mal de tête. Le bilan médical a révélé un cancer de la glande parotide droite aussi bien que des métastases pulmonaires. Elle a reçu une radiothérapie à visée palliative de la tumeur primaire. La patiente n’a reçu ni chimiothérapie ni immunothérapie. Pourtant, la tumeur primaire et toutes les métastases pulmonaires se sont résolues. La patiente est restée sans maladie clinique pendant environ un an avant la récidive. Ce cas clinique représente un des cas peu fréquents de la résolution abscopale d’un cancer métastatique après une radiothérapie en l’absence d’immunomodulation pharmacologique. Une analyse documentaire passe en revue l’histoire de l’effet abscopal de la radiothérapie, cherchant à déterminer les mécanismes de ses succès et de ses échecs et suggérant de nouvelles approches qui pourraient améliorer le taux de réussite de la combinaison de la radiothérapie et de l’immunothérapie.
Diffuse large B-cell lymphoma of the orbit: Clinicopathologic, immunohistochemical, and prognostic features of 20 cases
2012, American Journal of Ophthalmology
Citation Excerpt :
For example, B-cell biomarkers vary from tumor to tumor. Selective or exclusive involvements of different extranodal sites (testes, bowel, among others) can be seen, implying a set of cell surface receptors that can interact with tissue-specific antigens.27 DLBCL can arise de novo or be associated with states of immunodeficiency precipitated by disease or medications (methotrexate, fludarabine).3,28,29
To evaluate a series of orbital diffuse large B-cell lymphomas (DLBCL) for prognostic features and therapeutic outcomes.
Retrospective multicenter case study of clinical and immunohistochemical features of 20 patients.
Clinical, histopathologic, and immunohistochemical features were correlated with outcomes. Immunohistochemistry for biomarkers including Bcl-6, CD5, CD10, CD20, FOXP1, GCET1, and MUM1 was performed to differentiate between 2 major genetic subtypes of DLBCL: activated B-cell-like (ABC) and germinal center B-cell-like (GCB).
Sixteen patients presented with unilateral and 4 with bilateral tumors. Three had bony erosion of the orbit on imaging studies. Of 14 patients with detailed follow-ups, 3 had a prior or concurrent lymphomatous disease; 8 had stage I disease (limited to the orbit) at presentation; and 3 were newly diagnosed with systemic (stage IV) DLBCL. Localized disease was treated with combined systemic chemotherapy, including rituximab and radiation with no deaths to date; there was 1 death related to systemic DLBCL. Clinical staging was the best predictive method and no immunohistochemical feature or subcategory (ABC vs GCB) correlated with outcome.
Primary orbital DLBCL has a more favorable prognosis than systemic DLBCL and may arise from a preexistent hematolymphomatous neoplasm (4 out of 20 cases). In our series, orbital DLBCL had a 57% likelihood of being restricted to the ocular adnexa. Clinical staging was more helpful in predicting outcome than any single immunohistopathologic feature or combination of biomarkers. Orbital radiation of 30 gray in conjunction with systemic chemotherapy with rituximab can achieve disease-specific survival approaching 100% in purely localized cases.
Ocular Adnexal Lymphoid Tumors: Progress in Need of Clarification
2008, American Journal of Ophthalmology
Citation Excerpt :
There are two fundamental ways of looking at OALs: from the perspective of putatively predictive features that may be distinctive to the local lesions, or from the perspective of how OALs relate to better characterized systemic nodal and extranodal tumors. The ultimate goal is to find any parameter7—architectural, histopathologic, cytologic, precise anatomic localization, T-cell and B-cell composition, expanded immunophenotypic profiling, gene rearrangements, chromosomal translocations, transcription factors, nonimmunoglobulin cell-surface receptors, so-called homing or ecotaxic receptors,8 detectable traces of infectious agents9—that establish the origin, course, prognosis, and long-term clinical outcome. In other words, which OALs are primary, that is, arising in the ocular adnexa, and are likely to remain localized after appropriate therapy (usually radiotherapy), and which herald or are concurrently discovered to be part of a systemic disease?
To evaluate recent ophthalmic publications on ocular adnexal lymphomas (OALs) according to histopathologic and immunophenotypic criteria used in the diagnosis of systemic lymphomas (World Health Organization classification).
Summary and critical analysis of recent clinical and pathologic studies.
Literature review and interpretation.
In the largest study of 353 cases of OALs published in the pathology literature, extranodal marginal zone lymphoma (EMZL) constituted 52%, follicular lymphoma 23%, mantle cell lymphoma 5%, and small cell lymphocytic and chronic lymphocytic leukemia 4%—plus a residuum of arcane entities. In smaller series of less intensively studied OALs in the ophthalmic literature, EMZLs had a higher preponderance and also were associated with a favorable prognosis. Many EMZLs seemed to arise primarily in the ocular adnexa (mucosa-associated lymphoid tissue [MALT] lymphoma should be restricted for EMZLs involving epithelial tissues).
Rigorous diagnostic criteria and a proposal for a prospective multicenter study may bring further clarification to the emerging order in this set of tumors.
Hypothesis: symmetrical cutaneous lymphoma
1990, The Lancet
Patients with malignant lymphoma may have cutaneous and subcutaneous involvement that exhibits a striking symmetry about the coronal axis. The symmetry of these lesions may be caused by site-specific migration from the circulation, preferential proliferation by lymphocytes of the neoplastic clones at defined anatomical sites, or both mechanisms. Similar behaviour by benign lymphocytes may explain the symmetry and selective anatomical distribution of lesions in other skin diseases.
8 Immunology of gastrointestinal lymphoma
1987, Bailliere's Clinical Gastroenterology
Experimental work showing that IgA plasma cell precursors activated in gut associated lymphoid tissue (GALT) of rats and sheep migrate to the lamina propria of the gut via the regional lymphatics, mesenteric lymph node and blood, has been supported by immunohistochemical studies. In rats, immunoblasts with cytoplasmic IgA are present in the Peyer's patches in association with the high endothelial venules which is probably an important, though not the only, site of extravasation into the gut, whereas cells with cytoplasmic IgA are rarely observed in the dome regions of Peyer's patches. Immunohistochemical studies of human Peyer's patches have revealed differences between the distribution of cells with cytoplasmic IgA in man compared to rats. In man, immunoblasts with cytoplasmic IgA are not concentrated in the zone of cells containing the high endothelial venules, whereas they are present in the dome regions of the Peyer's patches. The following questions arise: Do precursors of IgA plasma cells activated in human GALT migrate to the lamina propria via the blood, but extravasate predominantly via the capillary network, rather than the high endothelial venules? or do IgA plasma cell precursors ‘mature’ in situ in the Peyer's patches of man and subsequently migrate laterally to seed the lamina propria? Three lines of evidence from studies of primary B cell lymphomas of GALT support the latter hypothesis: 1) Primary B cell lymphomas of the gut remain localized to GALT for long periods of time; 2) Histological studies of the lymphoid tissue in these lymphomas have shown a gradation of cell types, from the muscularis mucosae towards the mucosal epithelium, which strongly suggests that plasma cells develop in situ in the gut from the adjacent layers of cells; 3) Preliminary studies of DNA extracted from the blood-borne cells from patients with GALT-derived B cell lymphoma have failed to demonstrate the presence of clonal gene rearrangements.
Normal and malignant human GALT contains a perifollicular population of B cells with centrocyte-like morphology which lack surface IgD. No direct equivalent can be detected in rodent Peyer's patches. Their quiescent nature and distribution in malignant GALT suggests that they are follicle centre cell-derived and precursors of immunoblasts and plasma cells. As such they may be memory B cells. Their association with epithelium is a consistent feature of normal and malignant GALT which is of unknown but undoubted significance.
The function of intraepithelial T cells is still unknown. Malignant T cells in MHI may be derived from intraepithelial T cells. Further studies of these malignant T cells which are now in progress may enable a new approach to the investigation of human intraepithelial lymphocytes.
Ocular Adnexal Monoclonal Lymphoid Tumors with a Favorable Prognosis
1986, Ophthalmology
Fourteen patients with well- or intermediately differentiated monoclonal B-lymphocyec tumors of the conjunctiva or orbit had a favorable prognosis with follow-ups of 4 to 9 years (mean and median, 7.5 years). The lesions were, for the most part, diffuse proliferations of small lymphocytes, either with round or minimally indented nuclear outlines. Mitotic activity was sparse to nonexistent; occasionally there were scattered small abortive or residual germinal centers, and some lesions exhibited lymphoplasmacytoid features and dispersed multinucleated giant cells (polykaryocytes). None of the six patients with conjuncttval lesions had extraocular manifestations. An identical tumor of the submandibular gland developed in one of eight patients with orbital lesions and another patient had multiple extranodal involvements of the oropharynx, liver, and both kidneys, but after chemotherapy the patient has survived for 8 years from orbital presentation and is currently in remission. The authors believe that these low-grade tumors share many biologic resemblances to extranodal lymphoepithelial tumors of other organs (lung, gut, parotid, thyroid), which as a group have been aggregated together as mucosa-associated lymphoid tumors (MALT) and which can often remain localized to their sites of origin.

View all citing articles on Scopus

View full text

Hypothesis: HOMING OF LYMPHOCYTES TO NON-LYMPHOID TISSUES

Abstract

Blood

Lancet

Proc. R. Soc. B.

J. exp. Med.

Clin. exp. Immun.

Cancer