The impact of T-cell immunity on ovarian cancer outcomes.
Ovarian cancer remains a challenging disease for which improved treatments are urgently needed. Most patients present with advanced disease that is highly responsive to surgery combined with platinum- and taxane-based chemotherapy, with a state of minimal residual disease being achieved in many cases. However, chemotherapy-resistant recurrent tumors typically appear within 1-5 years and are ultimately fatal. Recently, several groups have shown that ovarian tumors are often infiltrated by activated T cells at the time of diagnosis, and patients with dense infiltrates of CD3+CD8+ T cells experience unexpectedly favorable progression-free and overall survival. Other cell types in the immune infiltrate oppose anti-tumor immunity, including CD4+CD25+FoxP3+ regulatory T cells, CD8+ regulatory T cells, macrophages, and dendritic cells. The composition of immune infiltrates is shaped by the expression of cytokines, chemokines, antigens, major histocompatibility complex molecules, and costimulatory molecules. The relationship between these various immunological factors is reviewed here with a strong emphasis on outcomes data so as to create a knowledge base that is well grounded in clinical reality. With improved understanding of the functional properties of natural CD8+ T-cell responses to ovarian cancer, there is great potential to improve clinical outcomes by amplifying host immunity.
Nelson
Brad H
BH
Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, BC, Canada. bnelson@bccancer.bc.ca
D015703:Antigens, CD / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D014408:Biomarkers, Tumor; D017252:CD3 Complex / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002986:Clinical Trials as Topic; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D018396:Mucin-1 / Q000276:immunology; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; C060192:MUC1 protein, human; D018396:Mucin-1; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor