Analysis of TCR usage in human tumors: a new tool for assessing tumor-specific immune responses

Sensi, Marialuisa; Parmiani, Giorgio

doi:10.1016/0167-5699(95)80082-4

Cited by 82 publications

(48 citation statements)

References 53 publications

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“…These results indicate that in vivo HLA-restricted cytotoxic T cell responses may occur at the tumor site. Since malignant melanoma nevertheless is one of the most malignant of tumors, it has been proposed that some tumor cells must escape this T cell response (13). Malignant melanoma in many cases show clear signs of regression in some parts whereas other parts of the same tumor show progression (14).…”

Section: Discussionmentioning

confidence: 99%

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Clonal T cell responses in tumor infiltrating lymphocytes from both regressive and progressive regions of primary human malignant melanoma.

Straten

Becker²,

Seremet³

et al. 1996

J. Clin. Invest.

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The T cell receptor (TCR) BV variable (V) gene repertoire of tumor infiltrating lymphocytes (TIL) found in progressive and regressive regions of the same primary human melanomas were characterized by reverse transcription coupled polymerase chain reaction (RT-PCR). After surgery, the tumors were divided into different parts which were judged as regressive or progressive regions by visual inspection. Subsequently this diagnosis was confirmed by histology. From a total of four primary melanomas analyzed, 2 were shown to be HLA-A2ϩ . Only relatively few BV-gene families were expressed at significant levels in each of the samples.

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Section: Discussionmentioning

confidence: 99%

“…It is therefore possible that future studies of TCR usage in HLA typed melanoma lesions may provide further information about the antigens giving rise to the major T cell responses against melanoma (13).…”

Section: Discussionmentioning

confidence: 99%

Clonal T cell responses in tumor infiltrating lymphocytes from both regressive and progressive regions of primary human malignant melanoma.

Straten

Becker²,

Seremet³

et al. 1996

J. Clin. Invest.

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“…In this context, preferential expansion of T cells with certain TCR BV regions has been observed frequently in patients with melanoma and other types of cancer. 30, 31 Saeterdal et al 14 found that a synthetic peptide from the melanoma protein gp100 [gp (9 280 )] was recognized by a number of T-cell clones using several different TCRs. The plethora of T-cell clones recognizing a single tumor peptide epitope could possibly increase tumor surveillance by the host immune system since induction of immune nonresponsiveness via anergy induction or clonal deletion of responding cells may affect some, but not all, of the respective clones.…”

Section: Discussionmentioning

confidence: 99%

HER‐2/neu–derived peptide epitopes are also recognized by cytotoxic CD3⁺CD56⁺ (natural killer T) lymphocytes

Baxevanis

Gritzapis

Tsitsilonis

et al. 2002

Intl Journal of Cancer

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The human HER-2/neu gene encodes a 185 kDa transmembrane glycoprotein recognized by MHC class I-restricted CTLs. Here, we report that HER-2/neu peptide CTL epitopes can also be recognized by cytotoxic NK-T lymphocytes. Unfractionated peptides derived from HLA-A2 Key words: natural killer T cells; cytotoxicity; cancer immunotherapy; HER-2/neu peptides; ovarian cancerCTLs recognize antigenic peptides, 8 -12 amino acid long, presented to them by professional APCs in the context of MHC class I molecules. 1 Such CTLs possess memory and can respond upon rechallenge by the same antigenic stimulus. Consequently, if induced by a tumor peptide vaccine, CTLs could provide longterm immunity. 2 Thus, definition of CTL peptide epitopes from tumor-associated antigens is an essential step toward the development of specific CTL-based cancer immunotherapy.It is now well established that CTLs recognizing human neoplastic cells can be isolated from PBMCs and tumor-infiltrating lymphocytes. 3 Such CTLs have been useful for identifying several genes encoding tumor antigens, which can be classified in the following groups: 3-5 (i) melanocyte differentiation antigens expressed on most melanoma cells and melanocytes but not on tumors from other tissues (e.g., tyrosinase, gp100, Melan-A/ MART-1); (ii) MAGE, BAGE and GAGE antigens expressed in several tumors of distinct histology but not in normal tissue except testis; (iii) unique, nonpublic tumor antigens generated by point mutations in widely expressed genes (e.g., cyclin-dependent kinase-4, ␤-catenin); and (iv) mutated (e.g., p53, k-ras), translocated (e.g., bcr-abl) and overexpressed (e.g., HER-2/neu) oncogenic proteins. Human therapeutic vaccine trials utilizing immunogenic CTL peptide epitopes are ongoing. 6 -9 While most of the focus in cancer immunology is on classical CD3 ϩ CD56 -CTLs, accumulating evidence suggests that CD3 ϩ cells coexpressing the NK cell marker CD56 display strong antitumor cytotoxic activity. Such cells normally comprise a small percentage of human PBLs (approx. 3%) and can be expanded in vitro in the presence of specific cytokine combinations. 10 Similar to lymphokine-activated killer cells, CD3 ϩ CD56 ϩ cells lyse their targets in a non-MHC-restricted manner but have demonstrated superior activity over lymphokine-activated killer cells since they show higher proliferation rates 11 and exert higher antitumor cytotoxic activity per culture, 11 higher purging activity against malignant cells derived from patients with chronic myelogenous leukemia 12 and higher cytotoxicity in a xenotransplant model. 13 A significant percentage of these CD3 ϩ CD56 ϩ cells did coexpress the CD8 antigen and this population was also highly cytotoxic. 13 In another report, 14 a melanoma peptide-specific, HLA-A2-restricted CTL clone of the same phenotype (i.e., CD3 ϩ CD56 ϩ CD8 ϩ ) appeared to belong to this subset of cells as it demonstrated both CTL and NK lytic ability.ACE isolated from tumor cell lysates contains peptides capable of specifically stimulating both CD4 ϩ and CD...

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“…T cell clonality analysis by clonotype mapping, cloning of TCR sequences, and spectra typing have demonstrated highly clonal expansion of TIL [13], skewed usage of some Vb subsets [14], and the diversity of the TCR repertoire [15]. However, the specificity, surveillance, and local accumulation of the overall panel of TCR V regions in tumors have been poorly investigated.…”

Section: Introductionmentioning

confidence: 99%

Clonal dynamics of tumor-infiltrating lymphocytes

Yu¹,

Fujio²,

Tahara³

et al. 2005

Eur. J. Immunol.

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The presence of tumor-infiltrating lymphocytes (TIL) provides important evidence of anti-tumor immunity in vivo. However, TIL are usually not sufficient for inhibiting tumor growth. We explored the spatial and temporal aspects of clonal accumulation of TIL using RT-PCR/single-strand conformation polymorphism analysis. In CMS5 fibrosarcomas in BALB/c mice, accumulated T cell clones were specific in that dominant TIL were identical between distant tumors. Moreover, dominant TIL in the first tumor appeared consistently in the second tumor inoculated after formation of the first tumor. These results suggest that TIL show a certain level of specific tumor surveillance. When we characterized CD4 + and CD8 + TIL separately, CD8 + TIL were highly concentrated and persistently localized at the tumor site, while most CD4 + TIL clones were less concentrated and less persistent. A functional analysis showed that TIL had a certain degree of anti-tumor activity when CD4 + and CD8 + TIL were cotransferred. Co-transfer of CD4 + and CD8 + TIL exhibited equivalent anti-tumor activity, irrespective of tumor stage. However, the numbers of TIL did not increase after the early phase of tumor progression. These data suggest that TIL are specific to the tumor and potentially retain anti-tumor activity, although their accumulation in mice is impaired.

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Analysis of TCR usage in human tumors: a new tool for assessing tumor-specific immune responses

Cited by 82 publications

References 53 publications

Clonal T cell responses in tumor infiltrating lymphocytes from both regressive and progressive regions of primary human malignant melanoma.

Clonal T cell responses in tumor infiltrating lymphocytes from both regressive and progressive regions of primary human malignant melanoma.

HER‐2/neu–derived peptide epitopes are also recognized by cytotoxic CD3⁺CD56⁺ (natural killer T) lymphocytes

Clonal dynamics of tumor-infiltrating lymphocytes

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Analysis of TCR usage in human tumors: a new tool for assessing tumor-specific immune responses

Cited by 82 publications

References 53 publications

Clonal T cell responses in tumor infiltrating lymphocytes from both regressive and progressive regions of primary human malignant melanoma.

Clonal T cell responses in tumor infiltrating lymphocytes from both regressive and progressive regions of primary human malignant melanoma.

HER‐2/neu–derived peptide epitopes are also recognized by cytotoxic CD3+CD56+ (natural killer T) lymphocytes

Clonal dynamics of tumor-infiltrating lymphocytes

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Product

Resources

About

HER‐2/neu–derived peptide epitopes are also recognized by cytotoxic CD3⁺CD56⁺ (natural killer T) lymphocytes