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

Hutchinson, Gill; Heinemann, D. E. H.; Symes, M. O.; Williamson, R. C. N.

doi:10.1038/bjc.1981.197

Cited by 26 publications

(10 citation statements)

References 15 publications

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“…However, the immune defence, if it was ever raised, appears to have deteriorated at least locally by the time tumours develop into clinically detectable lesions. This is in good agreement with the generally found suppression of various immune activities of tumour-infiltrating mononuclear cells (MNCs) (Nind et al, 1973;Klein et al, 1980;Bland et al, 1981;Hutchinson et al, 1981;Vose et al, 1981Vose et al, , 1982Vose and Moore, 1985;Miescher et al, 1986). Such immunosuppression may be mediated by tumour-derived factors or subsets of MNC.…”

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confidence: 75%

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

Håkansson

Adell²,

Boeryd³

et al. 1997

Br J Cancer

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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.

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confidence: 75%

“…This may indicate that the local immunosuppression is reversible (Klein et al, 1980;Hutchinson et al, 1981;Vose and Moore, 1985;Rosenberg et al, 1986). …”

mentioning

confidence: 99%

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

Håkansson

Adell²,

Boeryd³

et al. 1997

Br J Cancer

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“…Until recently, functional studies of human TIL were not feasible due to the paucity of these cells in tumor cell suspensions [22]. In a few cases where it was possible to examine proliferative and cytotoxic activities of human TIL, they were found to be depressed [4,9,11]. More recent availability of a T cell growth factor (TCGF) facilitated studies of human TIL and their in vitro culture [21].…”

Section: Discussionmentioning

confidence: 99%

Cytolytic antitumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes in recombinant interleukin 2

Whiteside

Heo

Takagi

et al. 1988

Cancer Immunol Immunother

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Lymphocytes infiltrating human solid tumors (TIL) and autologous peripheral blood lymphocytes (A-PBL) were cultured with 1000 units/ml of recombinant interleukin 2 (rIL2) in long-term cultures. TIL isolated from 26 primary squamous cell carcinomas of the head and neck expanded better (P less than 0.01) and achieved higher total lytic units of activity against fresh tumor cell targets (P less than 0.05) than A-PBL. TIL obtained from primary hepatocellular carcinomas (n = 7) showed a higher degree of expansion than those from metastatic liver tumors (n = 7). Further, TIL from metastatic tumors of the head and neck, liver, and ovary were delayed up to 50 days in their proliferative response to rIL2. Long-term mass cultures in rIL2 of TIL, A-PBL, or normal PBL were serially monitored for cytotoxicity with different cultured and fresh tumor cell targets and for phenotypic markers of the predominating cell populations. Antitumor cytotoxicity was found in cultures enriched in CD3+Leu19+ and/or CD3-Leu19+ cells. Two-color sorting of such cultures followed by cytotoxicity assays confirmed that the human antitumor effectors expressed either the CD3+Leu19+ or CD3-Leu19+ phenotype. CD3+Leu19- cells had little or no antitumor cytotoxicity. The two types of Leu19+ effector cells were present in low numbers in fresh TIL, A-PBL, or normal PBL; in contrast, in some rIL2-expanded long-term cultures, they represented a majority of proliferating cells. This study identifies for the first time two types of antitumor effector cells in rIL2 cultures of human TIL, one of which may represent activated natural killer cells on the basis of the absence of the CD3 and expression of the Leu19 antigen. These antitumor effector cells mediate non-MHC-restricted cytotoxicity of fresh or cultured tumor cell targets of different histologic types.

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“…Extensive testing of similar freshly derived tumourcell suspensions has shown that they are largely refractory to NK-mediated lysis and minimally express the relevant recognitive structure (Vose & Moore, 1980). As such they share with the short-term cultures of Nairn and associates (Nairn et al, 1971;Pihl et al, 1976) the property of permitting the measurement of specific effector function (Werkmeister et al, 1979 (Hutchinson et al, 1981). 58 In situ there is evidence that these cells have suppressor activity, and are less responsive to mitogens than PBL (Vose & Moore, 1979).…”

Section: Discussionmentioning

confidence: 99%

Specific and non-specific lymphocyte cytotoxicity in colon carcinoma

Vose¹,

Gallagher²,

Moore³

et al. 1981

Br J Cancer

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The cytotoxic activity of peripheral-blood (PBL), lymph-node (LNC) and tumour-infiltrating lymphocytes (TIL) from 47 patients undergoing surgery for colon carcinoma (Duke's Stage A, 1 patient; B, 24; C, 15 and C with metastases, 7) was examined in short-term 51Cr-release assays, against fresh autologous tumour cells, allogeneic colon cancer cells and the erythroleukaemia cell line, K562. Cytotoxicity against autologous cells was detected in at least one effector population in 23/47 patients (49%), with overall frequencies which did not differ for patients in different Duke's stages of disease. By contrast, lysis of allogeneic tumour cells was infrequent (11%) regardless of the effector population to which they were exposed. Cytotoxicity against K562, cells highly sensitive to NK activity, though variable, was detected in 93% of PBL of normal donors and 83% of patients, and among the latter showed no evidence of significant decline with advancing disease. However, LNC and TIL anti-K562 activity was infrequent (17%) in concordance with previous reports. There was no correlation between the ability of patients' PBL to lyse autologous tumour and K562 cells. The independence of these 2 cytotoxic actions was further explored in studies fractionating lymphocytes: autologous tumour killing was augmented in T-enriched PBL; whereas the greatest anti-K562 activity was found in the corresponding non-T fraction. Lymphocyte cytotoxicity in colonic neoplasia is thus manifest in 2 apparently independent lymphocyte populations; a relatively specific killer T-cell population, detectable in PBL, LNC and TIL, which is preferentially reactive with the autologous cells; and a non-specific killer population, largely limited to PBL, with the properties of NK cells. The activity of neither population reflects the clinical status of patients with this disease.

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

Cited by 26 publications

References 15 publications

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

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

Cytolytic antitumor effector cells in long-term cultures of human tumor-infiltrating lymphocytes in recombinant interleukin 2

Specific and non-specific lymphocyte cytotoxicity in colon carcinoma

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