Patterns of Human Tumor-Infiltrating Lymphocytes in 120 Human Cancers

Balch, Charles M.; Riley, Lee B.; Bae, Yoon Joo; Salmeron, Marie A.; Platsoucas, Chris D.; Eschenbach, Andrew von; Itoh, Kyogo

doi:10.1001/archsurg.1990.01410140078012

Cited by 235 publications

(152 citation statements)

References 21 publications

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“…Consistent with previous studies [5,21,22], our three-colour immunofluorescence analyses revealed that primary RCC tumours are predominantly infiltrated by T cells (> 60% of TIL in 16 of 20 tumour samples). Interestingly, we observed that an important proportion of CD3 þ TIL consists of double-positive CD4 þ CD8 þ T cells.…”

Section: Discussionsupporting

confidence: 92%

“…Since the origin of double-positive CD4 þ CD8 þ TIL in RCC remains to be established, this subset should at present be considered as a separate TIL population. Although some groups reported a predominance of CD4 þ tumour-infiltrating T cells in RCC [5,21], we and others [6,23] observed a clear predominance of CD3 þ CD8 þ TIL. In the present study only three of 20 tumour samples (15%) contained a (marginally) higher proportion of CD3 þ CD4 þ than CD3 þ CD8 þ TIL.…”

Section: Discussioncontrasting

confidence: 70%

“…Second, about 15-20% of patients with advanced RCC respond to systemic IL-2 administration, and durable (> 60 months) responses with complete disappearance of all measurable disease have been achieved in some patients with metastatic disease [3,4]. Third, RCC tumours are more heavily infiltrated by lymphocytes than other cancers [5] and contain expansions of clonal T cell populations, which have been considered to be part of the host immune response against the tumour and to be enriched in T cells with tumour specificity [6,7]. Finally, MHC-restricted, RCC-specific cytotoxic T cells have been identified among tumour-infiltrating lymphocytes (TIL) of some patients [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma

Hove¹,

Gool²,

Poppel³

et al. 1997

Clinical and Experimental Immunology

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SUMMARYWe investigated the phenotype and functional capacities of tumour-infiltrating lymphocytes (TIL), freshly isolated from primary renal cell carcinoma (RCC) specimens (n ¼ 20). Three-colour flow cytometry immunophenotyping revealed that RCC TIL consist mainly of CD3 þ T cells, with a clear predominance of CD4 ¹ CD8 þ over CD4 þ CD8 ¹ T cells, and a marked population of CD4 þ CD8 þ T cells. Natural killer (NK) cells were also strongly represented (> 25% in 15 of 20 tumour samples), while B cells constituted a minor TIL subset (< 5% in 18 of 20 tumour samples). More importantly, the T and NK cells within the tumour displayed a significantly higher expression of the early activation marker CD69 than their counterparts in adjacent normal renal tissue and in peripheral blood. Expression of CD54 and of HLA-DR was also elevated on CD3 þ TIL, and HLA-DR expression was further vigorously up-regulated following ex vivo stimulation with anti-CD3, all suggesting enhanced immune activity within the tumour microenvironment. CD3 þ CD4 þ TIL displayed a normal capacity to up-regulate CD25 expression and to secrete both Th1-type (IL-2, tumour necrosis factor-alpha (TNF-a) and interferon-gamma (IFN-g)) and Th2-type (IL-4, IL-5 and IL-10) cytokines upon triggering with anti-CD3. Furthermore, cytokine production was susceptible to modulation by CD28 costimulation. CD3 þ CD8 þ TIL, on the other hand, consistently demonstrated a poor up-regulation of CD25 upon triggering with anti-CD3, and displayed poor ex vivo cytolytic activity in an anti-CD3-redirected 4-h cytotoxicity assay against murine P815 cells. Collectively, our findings indicate that the CD3 þ CD4 þ TIL in RCC have normal functional capacities, whereas the proportionally major CD3 þ CD8 þ TIL are functionally impaired. The relevance of these findings to the in vivo local immune response in RCC is discussed.

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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Phenotype, cytokine production and cytolytic capacity of fresh (uncultured) tumour-infiltrating T lymphocytes in human renal cell carcinoma

Hove¹,

Gool²,

Poppel³

et al. 1997

Clinical and Experimental Immunology

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“…It is well recognised that human cancer tissues are infiltrated with tumour-infiltrating lymphocytes (TIL) (Balch et al, 1990), a phenomenon known to be a manifestation of the host immune reaction to cancer cells (Rosenberg, 1996). Tumourinfiltrating lymphocytes has been reported to be associated with improved prognosis of some carcinomas, including lung (DiPaola et al, 1977) and colon (Naito et al, 1998) carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Expression of EBAG9/RCAS1 is associated with advanced disease in human epithelial ovarian cancer

Aoki

Suzuki

et al. 2004

Br J Cancer

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Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription -polymerase chain reaction (RT -PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERa. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERa were evaluated by RT -PCR in 22 cases. The expression for EBAG9 and ERa was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P ¼ 0.0402) and advanced disease (P ¼ 0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P ¼ 0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (Po0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERa mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERa expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.

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“…Recent in vitro experiments show that tumour-infiltrating lymphocytes have little or no cytotoxic activity against autologous tumour (Balch et al, 1990), and that their function may be inhibited by tumour cells (Miescher et al, 1986). On the other hand, inflammatory cells are a potentially important source of cytokines that may affect angiogenesis and of enzymes that digest the extracellular matrix and thus may affect tumour growth and metastasis.…”

mentioning

confidence: 99%