A new class of anticancer agents can restore the ability of cytotoxic T lymphocytes (CTLs) to infiltrate the tumor and kill target cells in patients with metastatic non-small cell lung cancer (mNSCLC). This new precision medicine approach involves programmed cell death receptor-1 (PD-1) and human leukocyte antigen (HLA) molecules
PD-1 Blockade alone, or in combination with chemotherapy is a very active and promising immunotherapy for mNSCLC. However, it may be very expensive, and in some cases associated with severe immunological adverse events (irAEs), with no reliable biomarkers to distinguish potentially responsive patients versus those susceptible to complications.
A promising study recently published on the prestigious Journal of Immunotherapy of Cancer by the international Group led by the Prof. Pierpaolo Correale of the Medial Oncology Unit, Grand Metropolitan Hospital in Reggio Calabria, Italy; Prof. Michele Caraglia of the Biochemistry section, University “Vanvitelli” of Naples, Italy; Prof. Pierosandro tagliaferri of the Medical Oncology Unit, University of Catanzaro, Italy; and Prof. Antonio Giordano, Founder and Director of the Sbarro Health Research Organization (SHRO) at Temple University, Philadelphia and the department of Pathology at University of Siena, Italy, described the critical role played by class I and II HLA allele gene characterization in predicting nivolumab efficacy in mNSCLC and provided the rationale for further prospective trials of cancer immunotherapy.
The authors say: “We took in consideration that either the treatment response or the immunological adverse events correlated with these agents derive by their ability of reactivating tumor specific killers within the tumor environment. These Killer cells designated as Cytotoxic T lymphocytes are able to recognize tumor cells expressing anomalous molecular structures designated as antigens. T cells express use a specific receptor (T cell receptor) to engage part of these antigens exposed by HLA molecules on the membrane of target cells. Each individual presents different class I/II HLA gene alleles inherited by his/her parents with distinctive ability in binding and presenting tumor antigens. On these basis it was performed a multi-institutional retrospective analysis aimed to evaluate the genetic susceptibility to the response of a cohort of 119 patients who received treatment with PD-1 immune-checkpoint inhibitors identifying specific HLA alleles correlated with both response and immune-related adverse events”.
The authors continue: “If these data should be confirmed on a large series, it is reasonable to propose the combined use of ICB and allele-specific anticancer vaccines in patients who failed to enforce a poor spontaneous tumor antigen-specific immune response.
“Our results suggest that an accurate multimodal definition of tumor immunogenicity at baseline as well as a germline class I and II HLA allele characterization deserves to be studied on a large scale in these patients in a contest of Real World Evidence in order to define not only responsive patients but also patients with high risk of lethal irAEs and to propose new treatment modalities combining immune checkpoint inhibitors and class I HLA allele-specific anticancer vaccines.”
“Distinctive germline expression of class I human leukocyte antigen (HLA) alleles and DRB1 heterozygosis predict the outcome of patients with non-small cell lung cancer receiving PD-1/PD-L1 immune checkpoint blockade,” Correale P, et al. J Immunother Cancer 2020;8:e000733. doi:10.1136/jitc-2020-000733
About the Sbarro Health Research Organization
The Sbarro Health Research Organization (SHRO) is non-profit charity committed to funding excellence in basic genetic research to cure and diagnose cancer, cardiovascular diseases, diabetes and other chronic illnesses and to foster the training of young doctors in a spirit of professionalism and humanism. To learn more about the SHRO please visit www.shro.org
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