Melanoma biomarkers: Predicting the clinical outcome of immunotherapy

Davide Bedognetti, Ena Wang, Mario Roberto Sertoli, Francesco M. Marincola

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Tumor immunology is a mysterious land where the intricacy of the polymorphic human immunology combines with the complex biology of cancer. Experimental models created to bypass such complexity by inbreeding animals and standardizing cancers miss such basic essence. The complexity of several and redundant molecular pathways responsible for the natural and/or treatment-induced behavior of tumors cannot be analyzed by just hypothesisdriven approaches. The great majority of studies did not find any correlation between the development of immunity to the antigen administered and clinical outcomes. The observation that the generation of tumor antigen-specific immune responses may be necessary but most often insufficient to induce cancer rejection has led to the development of a novel approach capable to investigate the tumor/host integration in its globalism. After treatment with IL-2, the inflammatory stimuli at tumor size may induce the coordinate activation of several immune-modulators and immune-effector genes that switch on the dormant host's immune system with consequent generation of an effective tumor rejection. This switch is more likely to occur in tumors with a pre-existing inflammatory status. Post-treatment factor predictive of response and/or of clinical outcome to immune therapies include: development of autoimmunity (anti-CTLA-4 monoclonal antibody, IL-2 and adjuvant IFN-α), a greater increase of leukocyte count (IL-2, anti-CTLA-4 monoclonal antibody) or FOXP3 T regulatory cells (IL-2 ± vaccination), a stronger delay delayed-type hypersensitivity or epitope spreading (vaccination), persistence of the infused tumor-infiltrating lymphocytes in peripheral blood (adoptive therapy) (Tables 9.1-9.3). Pretreatment factor predictive of response and/or of clinical outcome to immune therapies include: CCR5 polymorphisms (immune chemotherapy, adoptive therapy), HLA polymorphisms (adjuvant IFN-α), CTLA-4 polymorphisms (anti-CTLA-4 monoclonal antibody), IFN-γ and IL-10 polymorphisms (immune chemotherapy), IL-10 serum level and intratumoral transcript (IL- 2/vaccine therapy), intratumoral expression of CXCR3 and/or CCR5 ligands and other proinflammatory cytokines or proinflammatory genes (IL-2, vaccination), intratumoral FOXP3 and IDO expression (anti-CTLA-4), VEGF or fibronectin serum level (IL-2), CXCR3 and CCR5 expression, telomere length and number of CD8+ CD27+ infused tumor-infiltrating lymphocytes (adoptive therapy), ratio of intratumoral pSTAT1/pSTAT3 (neoadjuvant IFN-α), inflammatory cytokines and chemokines serum level (adjuvant IFN002Da) (Table 9.4-9.6).

Original languageEnglish
Title of host publicationEmerging Therapeutics for Melanoma
PublisherFuture Medicine Ltd.
Pages121-152
Number of pages32
ISBN (Electronic)9781780840321
ISBN (Print)9781780841168
DOIs
Publication statusPublished - 1 Jan 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bedognetti, D., Wang, E., Sertoli, M. R., & Marincola, F. M. (2012). Melanoma biomarkers: Predicting the clinical outcome of immunotherapy. In Emerging Therapeutics for Melanoma (pp. 121-152). Future Medicine Ltd.. https://doi.org/10.2217/EBO.11.260