Separation and Characteristics of Tumor-Infiltrating Lymphocytes in Man

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis L HAkansson1, G Adell1, B Boeryd2, F Sjogren3 and R Sjodahl4Departments of 'Oncology, 2Pathology, 3Clinical Immunology and 4Surgery, University Hospital of Linkoping, S-581 85 Linkoping, Sweden Summary Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD1 1 c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC Il-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.

supporting

confidence: 86%

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Håkansson

Adell²,

Boeryd³

et al. 1997

“…also failed to demonstrate cytotoxicity of TIL for autologous tumour cells in 6 patients with a variety of neoplasms. Klein et al (1980) in similar experiments found TIL cytotoxic for autologous tumour celis in 10/39 cases, but none of these patients had colorectal cancer.…”

mentioning

confidence: 77%

Differential immune reactivity of tumour-intrinsic and peripheral-blood lymphocytes against autoplastic colorectal carcinoma cells

Hutchinson¹,

Heinemann²,

Symes³

et al. 1981

Summary.-Peripheral blood lymphocytes (PBL) were obtained from 13 patients and tumour-intrinsic lymphocytes (TIL) from 20 patients with colorectal cancer. The PBL were separated on a Ficoll-Isopaque gradient and the TIL by digestion of the tumour with collagenase-DNase. Both PBL and TIL were passed through nylonwool columns and the eluted cells were co-cultured for 2 h with 51Cr-labelled tumour cells from the same patient. If patients in whom spontaneous 51Cr release from the tumour cells was greater than 3300 were excluded, PBL showed cytotoxicity for the autoplastic tumour cells in 5/10 cases and TIL in 3/10 cases (NS). In 12 cases the cytotoxicity of the TIL was compared with that for TIL from the same tumour after the lymphocytes had been washed a further 6 times in Medium 199. Three effector: target (E/T) ratios, 5:1, 10:1 and 20:1, were used. The proportion of effector populations showing cytotoxicity was 2/12 for unwashed TIL and 9/12 for washed TIL (P<0.006). At the 5:1 E/T ratio the level of cytotoxicity was not significantly greater for washed TIL, but at the 10:1 ratio washed TIL showed significantly more cytotoxicity (P <0-025). At the 20:1 E/T ratio, a comparison was possible in 15 cases and the washed TIL again showed greater cytotoxicity (P<0-001).

“…2, top) patients. The use of collagenase on all the solid-tumour material and several of the ascites which had gelled is unlikely to have had any effect on these results as we (Haskill et al, 1982;Hayry & Totterman, 1978) cently there has been an increase in Klein et al (1980) Is have been isolated from human Hayry & Totterman (1978) have inmours (Mantovani et al, 1979;Werk- for 3 seminoma patients. The ANAE T-cell subset was the most prominent subset in the isolate.…”

Section: Proportions Of Inflammatory: Tumour Cells In Ascites and Tummentioning

confidence: 87%

“…Although there is a consensus that, for a variety of cancers in situ, immunity may be important to clinical response (Underwood, 1974;loachim, 1976), there has yet to be a study which directly implicates immune-dependent cellular mechanisms in growth control of cancer. Recently, a number of reports have described attempts to characterize the immunological competence of lymphocytes or macrophages isolated from human cancers or ascites (Mantovani et al, 1979;Werkmeister et al, 1979;Totterman et al, 1980;Klein et al, 1980;Herberman et al, 1980;Vose, 1978).…”

mentioning

confidence: 99%

Mononuclear-cell infiltration in ovarian cancer. I. Inflammatory-cell infiltrates from tumour and ascites material

Haskill¹,

Becker²,

Fowler³

et al. 1982

Malignant effusions and tumour tissue obtained at surgery provided material for a study of the prognostic value of the various inflammatory cells in the prognosis of human ovarian cancer. Ascitic fluids predominantly contained inflammatory cells; tumour cells, both singly and in clusters, were a minor component. Tumour cells were usually in excess in dispersed solid material. Some patients had significant proportions of lymphocytes and macrophages in their solid tumour, and these patients invariably responded to therapy. Sedimentation-velocity separation at unit gravity provided tow populations of inflammatory cells. One consisted of mononuclear cells similar in size to those in the patients blood: the other consisted of one or more large macrophage populations, distinct in morphology and enzymatic markers from both blood monocytes and each other. T lymphocytes were enriched in ascites fractions (78%) and in the tumour-derived mononuclear fraction (71%) compared to patient blood (60%). The T-cell subset characterized by ANAE reactivity was markedly depleted in the tumour-infiltrating fraction (17%) compared to patient blood (62%) or patient blood (51%). Esterase-positive monocyte-like cells were more frequent in the tumour-infiltrating fraction (17%) than ascites (7%) or blood (12%). B lymphocytes were infrequent in solid tumours and difficult to assess in ascites. Histiocyte-like macrophages were present in the higher-velocity tumour-cell containing fractions of both solid and ascitic material. The variation in infiltrating cells between patients and between tumour and ascites of the same individual was marked.