Neoantigen-directed immune escape in lung cancer evolution

Rosenthal, Rachel; Cadieux, Elizabeth Larose; Salgado, Roberto; Bakir, Maise Al; Moore, David A.; Hiley, Crispin; Lund, Tom; Tanić, Miljana; Reading, James L.; Joshi, Kroopa; Henry, Jake Y.; Ghorani, Ehsan; Wilson, Gareth A.; Birkbak, Nicolai J.; Jamal‐Hanjani, Mariam; Veeriah, Selvaraju; Szállási, Zoltán; Loi, Sherene; Hellmann, Matthew D.; Feber, Andrew; Chain, Benny; Herrero, Javier; Quezada, Sergio A.; Demeulemeester, Jonas; Loo, Peter Van; Beck, Stephan; McGranahan, Nicholas; Swanton, Charles

doi:10.1038/s41586-019-1032-7

Cited by 714 publications

(673 citation statements)

References 35 publications

Supporting

Mentioning

615

Contrasting

Unclassified

Order By: Relevance

“…Whereas the majority of early studies have prioritized single TCRs recognizing targets in the context of the common HLA‐A*02:01 allele (of North American and European Caucasian populations), only recently have investigators searched for TCRs restricted to other common alleles 123 . Priority targeting of known driver mutations, which are more likely to be clonal “trunk” mutations, will be advantageous so as to limit immune escape from antigen loss or incomplete clearance due to preexisting intratumor heterogeneity 124–126 . A final consideration for effective NeoAg‐specific therapies is that of optimal TCR avidity.…”

Section: Considerations For Neoag‐specific Therapiesmentioning

confidence: 99%

“…123 Priority targeting of known driver mutations, which are more likely to be clonal "trunk" mutations, will be advantageous so as to limit immune escape from antigen loss or incomplete clearance due to preexisting intratumor heterogeneity. [124][125][126] A final consideration for effective NeoAg-specific therapies is that of optimal TCR avidity. Studies employing minimally altered tumor epitopes to model varying TCR-MHC interaction strengths have demonstrated that vaccination with intermediate affinity epitopes provides optimal tumor control, whereas the highest affinity epitope vaccinations result in a dysfunctional T cell response.…”

Section: Considerations For Neoag-specific Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Harnessing neoantigen specific CD4 T cells for cancer immunotherapy

Brightman

Naradikian

Miller

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The goal of precision immunotherapy is to direct a patient's T cell response against the immunogenic mutations expressed on their tumors. Most immunotherapy approaches to‐date have focused on MHC class I‐restricted peptide epitopes by which cytotoxic CD8+ T lymphocytes (CTL) can directly recognize tumor cells. This strategy largely overlooks the critical role of MHC class II‐restricted CD4+ T cells as both positive regulators of CTL and other effector cell types, and as direct effectors of antitumor immunity. In this review, we will discuss the role of neoantigen specific CD4+ T cells in cancer immunotherapy and how existing treatment modalities may be leveraged to engage this important T cell subset.

show abstract

Section: Considerations For Neoag‐specific Therapiesmentioning

confidence: 99%

Section: Considerations For Neoag-specific Therapiesmentioning

confidence: 99%

Harnessing neoantigen specific CD4 T cells for cancer immunotherapy

Brightman

Naradikian

Miller

et al. 2020

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…2,9 In order to stimulate an antitumor immune response, neoantigens must be presented to T cells in the context of MHC molecules. Numerous sources of TAAs and neoantigens arise due to mutation of oncogenes and suppressor genes, re-expression of foetal proteins and oncogenic viral proteins, and/ or overexpression of normal proteins.…”

Section: Neoantigens and Vaccinationmentioning

confidence: 99%

The role and therapeutic implications of T cells in cancer of the lung

2019

View full text Add to dashboard Cite

Lung cancer remains the leading cause of cancer‐related death worldwide. The disease is classified into two major subtypes, small‐cell lung cancer (SCLC) and the more prevalent non‐small‐cell lung cancer (NSCLC). First‐line conventional therapies, such as chemotherapy, radiotherapy and surgery, have offered limited benefit, and patient prognosis remains poor with post‐treatment recurrences representing a major cause of morbidity. Consequently, there is an urgent need for improved therapeutic options. Historically, NSCLC has been considered a non‐immunogenic disease. However, increased understanding of tumor‐immune interactions has challenged this paradigm in both lung and other malignancies, with cancer elimination by tumor‐specific T cells increasingly well described in a myriad of solid tumors. Recent evidence has demonstrated that absent or weak anticancer responses are likely a product of tumor‐derived immunosuppression. This knowledge, along with a greater appreciation for the role of T cells in lung cancer elimination, has driven development of novel immunotherapeutic approaches which are demonstrating remarkable clinical efficacy. This review examines the role of T cells in lung cancer, discussing the direction and clinical significance of current and future immunotherapeutic strategies.

show abstract

“…The intratumoral heterogeneity (ITH) consequently gives rise to subclonal neoantigens. The link between neoantigen clonality and ICI effects has been reported, indicating the necessity of targeting clonal but not subclonal cancer antigens to maximize the effects of immunotherapy …”

Section: Immunoediting Antigen Clonality and Immunogenicitymentioning

confidence: 99%

“…The link between neoantigen clonality and ICI effects has been reported, indicating the necessity of targeting clonal but not subclonal cancer antigens to maximize the effects of immunotherapy. 26,27 Another important aspect of neoantigen research is related to their immunogenicity. As every HLA ligand with an altered amino acid does not elicit host T-cell responses, clarification of the rules and elements defining immunogenicity is of great importance.…”

Section: Immunoediting Antigen Clonality and Immunogenicitymentioning

confidence: 99%

Proteogenomic discovery of cancer antigens: Neoantigens and beyond

Kanaseki

Tokita

Torigoe

2019

Pathology International

View full text Add to dashboard Cite

Host T cells infiltrate the cancer lesion and contribute to patient survival. T cells recognize antigen peptides displayed by the cancer cell human leukocyte antigen (HLA) system. Cancer antigens constitute an essential element of T‐cell discrimination and play an indispensable role in anti‐cancer responses. HLA ligandome analysis directly and comprehensively detects the peptides that are naturally presented by HLA of given cells, leading to discovery of cancer antigens. A proteogenomic approach, which combines conventional proteomics with genomic information, has further deciphered the landscape of the cancer HLA ligandome. Neoantigens that arise from somatic mutations are arguably the major type of peptides patient T cells recognize. Moreover, cancer cells present peptides derived from alleged noncoding regions, which also elicit T‐cell responses thereby serving as cancer antigens. The diversity of newly discovered antigen sources implies that T cells are capable of sensing a variety of genomic aberrations in cancer.

show abstract

Neoantigen-directed immune escape in lung cancer evolution

Cited by 714 publications

References 35 publications

Harnessing neoantigen specific CD4 T cells for cancer immunotherapy

Harnessing neoantigen specific CD4 T cells for cancer immunotherapy

The role and therapeutic implications of T cells in cancer of the lung

Proteogenomic discovery of cancer antigens: Neoantigens and beyond

Contact Info

Product

Resources

About