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152. Exploiting the mutanome for tumor vaccination.

Author

Castle, J.C., Kreiter, S., Diekmann, J., Lower, M., Roemer, N. van de, Graaf, J. de, Selmi, A., Diken, M., Boegel, S., Paret, C., Koslowski, M., Kuhn, A.N., Britten, C.M., Huber, C., Tureci, O., Sahin, U., Castle, J.C., Kreiter, S., Diekmann, J., Lower, M., Roemer, N. van de, Graaf, J. de, Selmi, A., Diken, M., Boegel, S., Paret, C., Koslowski, M., Kuhn, A.N., Britten, C.M., Huber, C., Tureci, O., and Sahin, U.

Abstract

Item does not contain fulltext, Multiple genetic events and subsequent clonal evolution drive carcinogenesis, making disease elimination with single-targeted drugs difficult. The multiplicity of gene mutations derived from clonal heterogeneity therefore represents an ideal setting for multiepitope tumor vaccination. Here, we used next generation sequencing exome resequencing to identify 962 nonsynonymous somatic point mutations in B16F10 murine melanoma cells, with 563 of those mutations in expressed genes. Potential driver mutations occurred in classical tumor suppressor genes and genes involved in proto-oncogenic signaling pathways that control cell proliferation, adhesion, migration, and apoptosis. Aim1 and Trrap mutations known to be altered in human melanoma were included among those found. The immunogenicity and specificity of 50 validated mutations was determined by immunizing mice with long peptides encoding the mutated epitopes. One-third of these peptides were found to be immunogenic, with 60% in this group eliciting immune responses directed preferentially against the mutated sequence as compared with the wild-type sequence. In tumor transplant models, peptide immunization conferred in vivo tumor control in protective and therapeutic settings, thereby qualifying mutated epitopes that include single amino acid substitutions as effective vaccines. Together, our findings provide a comprehensive picture of the mutanome of B16F10 melanoma which is used widely in immunotherapy studies. In addition, they offer insight into the extent of the immunogenicity of nonsynonymous base substitution mutations. Lastly, they argue that the use of deep sequencing to systematically analyze immunogenicity mutations may pave the way for individualized immunotherapy of cancer patients.

Published
2012

153. Confidence-based Somatic Mutation Evaluation and Prioritization

Author

Lower, M., Renard, B.Y., Graaf, J. de, Wagner, M., Paret, C., Kneip, C., Tureci, O., Diken, M., Britten, C., Kreiter, S., Koslowski, M., Castle, J.C., Sahin, U., Lower, M., Renard, B.Y., Graaf, J. de, Wagner, M., Paret, C., Kneip, C., Tureci, O., Diken, M., Britten, C., Kreiter, S., Koslowski, M., Castle, J.C., and Sahin, U.

Abstract

Contains fulltext : 110677.pdf (publisher's version ) (Open Access), Next generation sequencing (NGS) has enabled high throughput discovery of somatic mutations. Detection depends on experimental design, lab platforms, parameters and analysis algorithms. However, NGS-based somatic mutation detection is prone to erroneous calls, with reported validation rates near 54% and congruence between algorithms less than 50%. Here, we developed an algorithm to assign a single statistic, a false discovery rate (FDR), to each somatic mutation identified by NGS. This FDR confidence value accurately discriminates true mutations from erroneous calls. Using sequencing data generated from triplicate exome profiling of C57BL/6 mice and B16-F10 melanoma cells, we used the existing algorithms GATK, SAMtools and SomaticSNiPer to identify somatic mutations. For each identified mutation, our algorithm assigned an FDR. We selected 139 mutations for validation, including 50 somatic mutations assigned a low FDR (high confidence) and 44 mutations assigned a high FDR (low confidence). All of the high confidence somatic mutations validated (50 of 50), none of the 44 low confidence somatic mutations validated, and 15 of 45 mutations with an intermediate FDR validated. Furthermore, the assignment of a single FDR to individual mutations enables statistical comparisons of lab and computation methodologies, including ROC curves and AUC metrics. Using the HiSeq 2000, single end 50 nt reads from replicates generate the highest confidence somatic mutation call set.

Published
2012

154. Cancer classification using the Immunoscore: a worldwide task force

Author

Galon, J, Pages, F, Marincola, FM, Angell, HK, Thurin, M, Lugli, A, Zlobec, I, Berger, A, Bifulco, C, Botti, G, Tatangelo, F, Britten, CM, Kreiter, S, Chouchane, L, Delrio, P, Arndt, H, Asslaber, M, Maio, M, Masucci, GV, Mihm, M, Vidal-Vanaclocha, F, Allison, JP, Gnjatic, S, Hakansson, L, Huber, C, Singh-Jasuja, H, Ottensmeier, C, Zwierzina, H, Laghi, L, Grizzi, F, Ohashi, PS, Shaw, PA, Clarke, BA, Wouters, BG, Kawakami, Y, Hazama, S, Okuno, K, Wang, E, O'Donnell-Tormey, J, Lagorce, C, Pawelec, G, Nishimura, MI, Hawkins, R, Lapointe, R, Lundqvist, A, Khleif, SN, Ogino, S, Gibbs, P, Waring, P, Sato, N, Torigoe, T, Itoh, K, Patel, PS, Shukla, SN, Palmqvist, R, Nagtegaal, ID, Wang, Y, D'Arrigo, C, Kopetz, S, Sinicrope, FA, Trinchieri, G, Gajewski, TF, Ascierto, PA, Fox, BA, Galon, J, Pages, F, Marincola, FM, Angell, HK, Thurin, M, Lugli, A, Zlobec, I, Berger, A, Bifulco, C, Botti, G, Tatangelo, F, Britten, CM, Kreiter, S, Chouchane, L, Delrio, P, Arndt, H, Asslaber, M, Maio, M, Masucci, GV, Mihm, M, Vidal-Vanaclocha, F, Allison, JP, Gnjatic, S, Hakansson, L, Huber, C, Singh-Jasuja, H, Ottensmeier, C, Zwierzina, H, Laghi, L, Grizzi, F, Ohashi, PS, Shaw, PA, Clarke, BA, Wouters, BG, Kawakami, Y, Hazama, S, Okuno, K, Wang, E, O'Donnell-Tormey, J, Lagorce, C, Pawelec, G, Nishimura, MI, Hawkins, R, Lapointe, R, Lundqvist, A, Khleif, SN, Ogino, S, Gibbs, P, Waring, P, Sato, N, Torigoe, T, Itoh, K, Patel, PS, Shukla, SN, Palmqvist, R, Nagtegaal, ID, Wang, Y, D'Arrigo, C, Kopetz, S, Sinicrope, FA, Trinchieri, G, Gajewski, TF, Ascierto, PA, and Fox, BA

Abstract

Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the 'Immunoscore' into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Tr

Published
2012

158. Styles and productivity of diapirism along the Middle America margin, Part II: Mound Culebra and Mounds 11, and 12

Author

Martinelli, G., Panahi, B., Moerz, T., Fekete, N., Kopf, A., Brueckmann, W., Sahling, H., Kreiter, S., Huehnerbach, V., Masson, D., Hepp, D.A., Schmitt, M., Kutterolf, S., Abegg, F., Spiess, V., Suess, E., Ranero, C.R., Martinelli, G., Panahi, B., Moerz, T., Fekete, N., Kopf, A., Brueckmann, W., Sahling, H., Kreiter, S., Huehnerbach, V., Masson, D., Hepp, D.A., Schmitt, M., Kutterolf, S., Abegg, F., Spiess, V., Suess, E., and Ranero, C.R.

Published
2005

162. Therapeutics

Author

Azimi, A., primary, Kuznecovs, S., additional, Kuznecovs, J., additional, Blazejczyk, A., additional, Switalska, M., additional, Chlopicki, S., additional, Marcinek, A., additional, Gebicki, J., additional, Wietrzyk, J., additional, Egyhazi, S., additional, Azimi, A., additional, Ghasghgaei, S., additional, Frostvik Stolt, M., additional, Hertzman Johansson, C., additional, Hansson, J., additional, Delage, J. D., additional, Li, H., additional, Lu, H., additional, Cazin, L. H., additional, Vannier, J. P., additional, Drouet, L., additional, Dupuy, E., additional, Soria, J., additional, Varin, R., additional, Soria, C., additional, Castle, J., additional, Kreiter, S., additional, Diekmann, J., additional, Lower, M., additional, van der Roemer, N., additional, de Graaf, J., additional, Selmi, S., additional, Diken, M., additional, Boegel, S., additional, Paret, C., additional, Koslowski, M., additional, Kuhn, A. N., additional, Britten, C. M., additional, Huber, C., additional, Tureci, O., additional, Sahin, U., additional, Procopio, G., additional, Verzoni, E., additional, Testa, I., additional, de Braud, F., additional, Misale, S., additional, Yaeger, R., additional, Hobor, S., additional, Scala, E., additional, Janakiraman, M., additional, Liska, D., additional, Valtorta, E., additional, Schiavo, R., additional, Buscarino, M., additional, Siravergna, G., additional, Bencardino, K., additional, Cercek, A., additional, Chen, C., additional, Veronese, S., additional, Zanon, C., additional, Sartore-Bianchi, A., additional, Gambacorta, M., additional, Gallicchio, M., additional, Vakiani, E., additional, Boscaro, V., additional, Medico, E., additional, Weiser, M., additional, Siena, S., additional, di Nicolantonio, F., additional, Solit, D., additional, Bardelli, A., additional, Burbridge, M. F., additional, Dovat, S. P., additional, Song, C., additional, Payne, K. J., additional, Yang, L., additional, Cree, A., additional, Glaysher, M., additional, Bolton, L., additional, Johnson, P., additional, Atkey, N., additional, Torrance, C., additional, Bogush, T. A., additional, Dudko, E. A., additional, Shaturova, A. S., additional, Tikhomirov, M. V., additional, Bogush, E. A., additional, Polotsky, B. E., additional, Tjulandin, S. A., additional, Davydov, M. I., additional, Pernemalm, M., additional, Pawitan, Y., additional, Lazar, V., additional, Lundeberg, J., additional, Lehtio, J., additional, Rasul, A., additional, Ma, T., additional, Dyshlovoy, S. A., additional, Naeth, I., additional, Venz, S., additional, Fedorov, S. N., additional, Shubina, L. K., additional, Stonik, V. A., additional, Balabanov, S., additional, Honecker, F., additional, Kongpracha, P., additional, Tohtong, R., additional, Demidkina, V., additional, Kudryavtsev, V. A., additional, Kabakov, A. E., additional, Golan, T., additional, Atias, D., additional, Barshack, I., additional, Avivi, C., additional, Goldstein, R. S., additional, Berger, R., additional, Ben-Arieh, S., additional, Urban, D., additional, Maimon, N., additional, Leibowitz-Amit, R., additional, Keizman, D., additional, Biran, H., additional, Mishaeli, M., additional, Onn, A., additional, Gottfried, M., additional, Saraswati, S., additional, Agrawal, S. S., additional, Raval, P., additional, Patel, M., additional, Ganure, L., additional, Hanen, J. H., additional, Sonia, B. H. K., additional, Aya, M., additional, Zohra, H., additional, Touhami, M., additional, Cheng, X., additional, Shi, T. Y., additional, Yang, G., additional, Tu, X. Y., additional, Wu, X. H., additional, Wei, Q. Y., additional, Benboubker, H., additional, Zheng, B. Q., additional, Shi, Y. Q., additional, He, X. H., additional, Liang, L. H., additional, and Saied, G. M., additional

Published
2012
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163. P2.06 Exploiting The Mutanome for Tumor Vaccination

Author

Castle, J., primary, Kreiter, S., additional, Diekmann, J., additional, Löwer, M., additional, van der Roemer, N., additional, de Graaf, J., additional, Selmi, S., additional, Diken, M., additional, Boegel, S., additional, Paret, C., additional, Koslowski, M., additional, Kuhn, A.N., additional, Britten, C.M., additional, Huber, C., additional, Türeci, Ö., additional, and Sahin, U., additional

Published
2012
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184. A new species of the genus Euseius Wainstein (Acari: Phytoseiidae) from France.

Author

Tixier, M.-S., Kreiter, S., Okassa, M., and Cheval, B.

Subjects
*PHYTOSEIIDAE, *MITES, *SPERMATHECA, *INSECT anatomy, *INSECT reproduction
Abstract

The identity of specimens belonging to the genus Euseius found on several trees in France is investigated. Previous molecular and morphological analyses have shown that the new species herein described is different from Euseius stipulatus. Among the 187 species belonging to the genus Euseius, four of them (Euseius querci, Euseius amissibilis, Euseius kirghisicus and Euseius longiverticalis) seem to be morphologically close to this new species. However, none were very similar. This paper reports the description of this new species: Euseius gallicus sp. nov. Kreiter and Tixier. [ABSTRACT FROM AUTHOR]

Published
2010
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186. Plants and Leaf Characteristics Influencing the Predaceous Mite Kampimodromus aberrans (Acari: Phytoseiidae) in Habitats Surrounding Vineyards.

Author

Kreiter, S., Tixier, M.-S., Croft, B. A., Auger, P., and Barret, D.

Subjects
PHYTOSEIIDAE, MITES, POLLEN, AGRICULTURAL pests, TRICHOMES
Abstract

We sampled phytoseiid mites (densities, diversity, and age structure) on several plants located in four uncultivated areas surrounding vineyards over 3 yr to determine how leaf structure affects populations. The plant composition of these areas greatly influenced the numbers and species of phytoseiids present. The relationships between leaf structure (trichome, pollen densities, number, and structure of domatia, leaf surface) and Kampimodromus aberrans (Oudemans) densities also were studied. The frequency of occurrence and the abundance of K. aberrans per cm2 were correlated to high trichome densities. A complex phylloplane (many hairs and shelters or domatia) could confer a competitive advantage to K. aberrans over other phytoseiid mite species. The number and the rating of domatia were important to K aberrans development; high proportions of immatures were observed only on plants with these structures. Pollen densities were significantly correlated to trichome densities; domatia structure had only a somewhat lesser effect. Our study shows that dense trichome and pollen levels are favorable to the development of K. aberrans populations and add perspective on the influence of domatia on this important predaceous mite. [ABSTRACT FROM PUBLISHER]

Published
2002
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187. The newborn examination: part II. Emergencies and common abnormalities involving the abdomen, pelvis, extremities, genitalia, and spine.

Author

Fuloria M and Kreiter S

Abstract

Careful examination of the neonate at delivery can detect anomalies, birth injuries, and disorders that may compromise successful adaptation to extrauterine life. A newborn with one anatomic malformation should be evaluated for associated anomalies. If a newborn is found to have an abdominal wall defect, management includes the application of a warm, moist, and sterile dressing over the defect, decompression of the gastrointestinal tract, aggressive fluid resuscitation, antibiotic therapy, and prompt surgical consultation. Hydroceles are managed conservatively, but inguinal hernias require surgical repair. A newborn with developmental hip dysplasia should be evaluated by an orthopedist, and treatment may require use of a Pavlik harness. The presence of ambiguous genitalia is a medical emergency, and pituitary and adrenal integrity must be established. Early diagnosis of spinal lesions is imperative because surgical correction can prevent irreversible neurologic damage. [ABSTRACT FROM AUTHOR]

Published
2002

188. The newborn examination: part I. Emergencies and common abnormalities involving the skin, head, neck, chest, and respiratory and cardiovascular systems.

Author

Fuloria M and Kreiter S

Abstract

The routine newborn assessment should include an examination for size, macrocephaly or microcephaly, changes in skin color, signs of birth trauma, malformations, evidence of respiratory distress, level of arousal, posture, tone, presence of spontaneous movements, and symmetry of movements. A newborn with one anatomic malformation should be evaluated for associated anomalies. Total and direct bilirubin levels should be measured in newborns with jaundice, and a complete blood count should be obtained in those with pallor or a ruddy complexion. Neurosurgical consultation is necessary in infants with craniosynostosis accompanied by restricted brain growth or hydrocephalus, cephaloceles, or exophytic scalp nodules. Neck masses can be identified by their location and include vascular malformations, abnormal lymphatic tissue, teratomas, and dermoid cysts. Most facial nerve palsies resolve spontaneously. Conjunctivitis is relatively common in newborns. Infants with chest abnormalities may need to be evaluated for Poland's syndrome or Turner's syndrome. Murmurs in the immediate newborn period are usually innocent and represent a transition from fetal to neonatal circulation. Because cyanosis is primarily secondary to respiratory or cardiac causes, affected newborns should be evaluated expeditiously, with the involvement of a cardiologist or neonatologist. [ABSTRACT FROM AUTHOR]

Published
2002

190. Morphological and steroidogenic changes in cultured adrenal tumor cells induced by a subunit of cholera enterotoxin

Author

Donta, S T, Kreiter, S R, and Wendelschafer-Crabb, G

Abstract

A purified subunit of the cholera enterotoxin molecule was found to have morphological and steroidogenic inducing effects similar to those induced by the native enterotoxin on monolayer tissue cultures of Y1 adrenal tumor cells, although 1,000 times more subunit than toxin (weight basis) was required for maximal effects. In contrast to the whole toxin, the effects of the active subunit could not be prevented by prior incubation with either Gm1 ganglioside or with antibodies directed against choleragenoid (the binding subunit). These results suggest that different receptor sites may exist on cells for the binding and for the active subunits of cholera enterotoxin and/or that the active toxin fragment may exert its effects after gaining access to the intracellular compartment.

Published
1976
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191. Comptes-rendus du colloque : 'Acariens des cultures'

Author

Kreiter, S., Brian, F., Valentin, G., and Moncomble, D.

Subjects
AMINOTRIAZOLE, TEST, TOXICITE, MIGRATION, REPULSION, ACARIEN PHYTOPHAGE, ADVENTICE, BIOLOGIE, GLYPHOSATE, PARAQUAT, VIGNE, PLANTE CULTIVEE, MESURE AU LABORATOIRE, RELATION HERBICIDE MIGRATION PLANTE CULTIVEE, ANIMAL NUISIBLE, HERBICIDE, ADAPTATION, GLUFOSINATE
Abstract

Les caractéristiques et les potentialités biologiques de #Tetranychus urticae$ et de #Tetranychus turkestani$ sont présentées afin de dégager leur capacité à envahir des milieux très variés. En viticulture, il est probable que l'évolution du mode de désherbage du sol du vignoble a permis un glissement adaptatif des acariens tisserands des mauvaises herbes vers la vigne, probablement accentué par une mauvaise utilisation de certains herbicides. Afin de dégager et de quantifier l'influence directe de ces produits sur les migrations de tétranyques, on a effectué une série de tests de laboratoire permettant de quantifier l'effet répulsif et toxique de quatre produits herbicides : aminotriazole, glufosinate, glyphosate, paraquat. Parallèlement, des essais ont été effectués en plein champ avec les mêmes produits. Les résultats obtenus font l'objet d'une autre communication par le troisième auteur. Les perspectives de travaux futurs sont évoqués. (Résumé d'auteur)

Published
1989

192. Colloque sur les acariens des cultures

Author

Bonato, Olivier, Cotton, D., Kreiter, S., and Gutierrez, Jean

Subjects
ACARIEN PHYTOPHAGE, DEVELOPPEMENT, FECONDITE, ETUDE EXPERIMENTALE, BIOLOGIE, TEMPERATURE, HYGROMETRIE, RESULTAT ANALYTIQUE
Published
1989

193. Les acariens, ravageurs mal connus du cyprès

Author

Gutierrez, Jean, Kreiter, S., Brian, F., and Cotton, D.

Subjects
ARBRE, LUTTE CHIMIQUE, ACARIEN PHYTOPHAGE, METHODE DE LUTTE, MORPHOLOGIE, CYCLE DE DEVELOPPEMENT, REPARTITION GEOGRAPHIQUE
Published
1986

194. Comptes-rendus du colloque : 'Acariens des cultures'

Author

Valentin, G., Moncomble, D., and Kreiter, S.

Subjects
TOXICITE, MIGRATION, RELATION HERBICIDE MIGRATION DYNAMIQUE DE POPULATION, ACARIEN PHYTOPHAGE, ADVENTICE, RELATION PLANTE HOTE ACARICIDE, VIGNE, PLANTE CULTIVEE, DATE D'INTERVENTION, LISERON, DYNAMIQUE DE POPULATION, ANIMAL NUISIBLE, PROTECTION, HERBICIDE, ACARICIDE, RELATION HERBICIDE ACARICIDE
Abstract

Pour réussir une application acaricide dirigée sur #T. urticae$, l'un des facteurs clés est la date d'intervention. Ces travaux illustrent parfaitement qu'elle est corrélée au traitement herbicide des plantes hôtes et notamment du liseron. Le glyphosate entraîne une migration brutale du ravageur sur la plante cultivée, ce qui accule le praticien à un traitement acaricide précoce. Le glufosinate retarde considérablement cette migration, alors que le paraquat est intermédiaire. L'effet toxique du glufosinate sur l'acarien Tisserand explique en partie cette observation et son emploi facilite grandement la lutte contre le prédateur. (Résumé d'auteur)

Published
1989

196. Actively personalized cancer vaccines--the step into clinical application

Author

Bp, Kloke, Kreiter S, Mathias Vormehr, Diken M, An, Kuhn, and Sahin U

Subjects
Neoplasms, Animals, Humans, RNA, Neoplasm, Cancer Vaccines
Abstract

Cancer vaccine development enters a new phase of innovation based on the development of modern sequencing technologies and novel RNA-based synthetic drug formats which enable the analysis and therapeutic targeting of every patient's tumor genome. By applying and combining these innovations, we have brought the concept of "actively personalized cancer vaccines" to clinical testing. Synthetic RNA is used as the drug format, allowing affordable, individual "on demand" manufacturing of tumor-optimized vaccines.

200. Cancer classification using the Immunoscore: a worldwide task force

Author

Galon Jérôme, Pagès Franck, Marincola Francesco M, Angell Helen K, Thurin Magdalena, Lugli Alessandro, Zlobec Inti, Berger Anne, Bifulco Carlo, Botti Gerardo, Tatangelo Fabiana, Britten Cedrik M, Kreiter Sebastian, Chouchane Lotfi, Delrio Paolo, Arndt Hartmann, Asslaber Martin, Maio Michele, Masucci Giuseppe V, Mihm Martin, Vidal-Vanaclocha Fernando, Allison James P, Gnjatic Sacha, Hakansson Leif, Huber Christoph, Singh-Jasuja Harpreet, Ottensmeier Christian, Zwierzina Heinz, Laghi Luigi, Grizzi Fabio, Ohashi Pamela S, Shaw Patricia A, Clarke Blaise A, Wouters Bradly G, Kawakami Yutaka, Hazama Shoichi, Okuno Kiyotaka, Wang Ena, O'Donnell-Tormey Jill, Lagorce Christine, Pawelec Graham, Nishimura Michael I, Hawkins Robert, Lapointe Réjean, Lundqvist Andreas, Khleif Samir N, Ogino Shuji, Gibbs Peter, Waring Paul, Sato Noriyuki, Torigoe Toshihiko, Itoh Kyogo, Patel Prabhu S, Shukla Shilin N, Palmqvist Richard, Nagtegaal Iris D, Wang Yili, D'Arrigo Corrado, Kopetz Scott, Sinicrope Frank A, Trinchieri Giorgio, Gajewski Thomas F, Ascierto Paolo A, and Fox Bernard A

Subjects
Medicine
Abstract

Abstract Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM classification) summarizes data on tumor burden (T), presence of cancer cells in draining and regional lymph nodes (N) and evidence for metastases (M). However, it is now recognized that clinical outcome can significantly vary among patients within the same stage. The current classification provides limited prognostic information, and does not predict response to therapy. Recent literature has alluded to the importance of the host immune system in controlling tumor progression. Thus, evidence supports the notion to include immunological biomarkers, implemented as a tool for the prediction of prognosis and response to therapy. Accumulating data, collected from large cohorts of human cancers, has demonstrated the impact of immune-classification, which has a prognostic value that may add to the significance of the AJCC/UICC TNM-classification. It is therefore imperative to begin to incorporate the ‘Immunoscore’ into traditional classification, thus providing an essential prognostic and potentially predictive tool. Introduction of this parameter as a biomarker to classify cancers, as part of routine diagnostic and prognostic assessment of tumors, will facilitate clinical decision-making including rational stratification of patient treatment. Equally, the inherent complexity of quantitative immunohistochemistry, in conjunction with protocol variation across laboratories, analysis of different immune cell types, inconsistent region selection criteria, and variable ways to quantify immune infiltration, all underline the urgent requirement to reach assay harmonization. In an effort to promote the Immunoscore in routine clinical settings, an international task force was initiated. This review represents a follow-up of the announcement of this initiative, and of the J Transl Med. editorial from January 2012. Immunophenotyping of tumors may provide crucial novel prognostic information. The results of this international validation may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Published
2012
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