Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy
Open accessAbstract
HLA genotype affects response: Immunotherapy works by activating the patient's own immune system to fight cancer. For effective tumor killing, CD8 + T cells recognize tumor peptides presented by human leukocyte antigen class I (HLA-I) molecules. In humans, there are three major HLA-I genes ( HLA-A, HLA-B , and HLA-C ). Chowell et al. asked whether germline HLA-I genotype influences how T cells recognize tumor peptides and respond to checkpoint inhibitor immunotherapies (see the Perspective by Kvistborg and Yewdell). They examined more than 1500 patients and found that heterozygosity at HLA-I loci was associated with better survival than homozygosity for one or more HLA-I genes. Thus, specific HLA-I mutations could have implications for immune recognition and for the design of epitopes for cancer vaccines and immunotherapies. Science , this issue p. 582 ; see also p. 516
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- Findingown data
In cohort 1, tumor loss of heterozygosity at HLA-I in patients heterozygous at all HLA-I loci was associated with reduced survival.
“Patients with LOH of HLA-I were associated with reduced survival (P = 0.05, HR = 1.60, 95% CI 1.03 to 2.43) (Fig. 1H).”
Quote in the paperSubstantial claim - Findingown data
In advanced melanoma patients treated with anti-CTLA-4, B62 alleles were associated with reduced overall survival.
“and patients with B62 alleles had significantly reduced survival (P = 0.0007, HR = 2.29, 95% CI 1.40 to 3.74) (Table 1).”
Quote in the paperSubstantial claim - Findingown data
In independent cohort 2, melanoma patients treated with anti-PD-1 or anti-CTLA-4 who carried B44 supertype alleles had better overall survival in univariate and multivariable analysis.
“In the independent cohort 2, melanoma patients treated with anti–PD-1 or anti–CTLA-4 who had these B44 supertype alleles had signif icantly better overall survival on univariate (P = 0.054, HR = 0.32, 95% CI 0.09 to 1.1) (Fig. 2, B and D) and multivariable analysis (tables S6 and S7).”
Quote in the paperSubstantial claim - Findingown data
On-therapy clonality of TCR CDR3s encoded by a single VJ cassette combination was higher in HLA heterozygotes.
“Higher on-therapy clonality of TCR CDR3s per VJ was observed in HLA heterozygotes (Wilcoxon rank-sum test, P = 0.023) (Fig. 3G).”
Quote in the paperSubstantial claim - Findingown data
One of six enriched amino acid mutations across these tumors was G > E.
“We found that one out of the six enriched amino acid mutations across these tumors was G > E (fig. S3).”
Quote in the paperNot a substantial claim
- Findingown data
The combined effect of HLA class I heterozygosity and mutation load on improved survival was greater than the effect of mutation load alone.
“The combined effect of HLA class I heterozygosity and mutation load on improved survival was greater as compared with mutation load alone (Fig. 1, F and G).”
Quote in the paperSubstantial claim - Findingown data
B44 alleles were not associated with survival in melanoma patients from The Cancer Genome Atlas.
“The B44 alleles did not associate with survival in patients with melanoma from The Cancer Genome Atlas (TCGA), suggesting that the presence of B44 was predictive of response to ICB and was not prognostic (Fig. 2I).”
Quote in the paperSubstantial claim - Findingown data
The HLA-DP homozygosity effect on survival was independent of HLA-I homozygosity and mutation burden.
“This effect was independent of the associations of HLA-I homozygosity and mutation burden (tables S4 and S5).”
Quote in the paperSubstantial claim - Findingown data
The B62 survival association was significantly driven by HLA-B*15:01.
“And, the B62 association was significantly driven by HLA-B*15:01 (P = 0.002, HR = 2.21, 95% CI 1.33 to 3.70) (Fig. 3A and Table 1).”
Quote in the paperSubstantial claim - Findingown data
On-therapy T cell receptor CDR3 clonality was higher in HLA heterozygous patients than in HLA homozygotes at at least one class I locus or HLA-DP.
“We found significantly higher on-therapy clonality of TCR CDR3s in HLA heterozygous patients as compared with HLA homozygotes (in at least one class I locus or at HLA-DP) (Wilcoxon rank-sum test, P = 0.0093) (Fig. 3F and table S1).”
Quote in the paperSubstantial claim - Findingown data
In advanced cancer patients treated with immune checkpoint blockade, homozygosity at one or more HLA class I loci is associated with shorter overall survival than heterozygosity at all HLA-I loci.
“Maximal heterozygosity at HLA-I loci (“A,” “B,” and “C”) improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus.”
- Also stated in: § Abstract · plain
“HLA-I homozygosity in at least one locus was associated with reduced survival in cohort 1 [n = 369 patients; P = 0.036, hazard ratio (HR) = 1.40, 95% confidence interval (CI) 1.02 to 1.9] (Fig. 1A) and was validated in the independent cohort of 1166 patients (cohort 2; P = 0.028, HR = 1.31, 95% CI 1.03 to 1.70) (Fig. 1B).”
- Also stated in: § Abstract · plain
“This analysis revealed that homozygosity at one HLA-I locus (“A,” “B,” or “C”) was associated with significant reduction of overall survival (P = 0.003, HR = 1.38, 95% CI 1.11 to 1.70) (Fig. 1C).”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
In advanced melanoma patients treated with anti-CTLA-4, B44 superfamily alleles were associated with better overall survival.
“Patients with B44 superfamily alleles had significantly better survival (P = 0.01, HR = 0.61, 95% CI 0.42 to 0.89) (Table 1)”
Quote in the paperSubstantial claim - Findingown data
The effect of HLA-I loss of heterozygosity on survival was greater in patients whose tumors had low mutation load.
“Furthermore, the effect of LOH of HLA-I on survival was greater in patients whose tumors contained low mutation load (P = 0.0006, HR = 3.68, 95% CI 1.64 to 8.23) (Fig. 1I).”
Quote in the paperSubstantial claim - Findingown data
In cohort 1 and cohort 2, the combination of HLA-I homozygosity and low tumor mutation burden was associated with worse survival than HLA-I heterozygosity and high mutation burden.
“We found that HLA-I homozygosity and low mutation burden were strongly associated with decreased survival compared with patients who were heterozygous at each class I locus and whose tumors had high mutation burden, in cohort 1 (P = 0.003, HR = 2.03, 95% CI 1.27 to 3.30) (Fig. 1D) and in cohort 2 (P < 0.0001, HR = 2.98, 95% CI 1.84 to 4.82) (Fig. 1E).”
Quote in the paperSubstantial claim - Findingown data
The effect of B44 alleles on extended survival was greater when somatic mutational load was also considered in cohort 1 and cohort 2.
“Furthermore, the effect of B44s on extended survival was greater when somatic mutational load was also considered in cohort 1 (P < 0.0001, HR = 0.23, 95% CI 0.13 to 0.41) (Fig. 2E) and in cohort 2 (P = 0.023, HR = 0.13, 95% CI 0.02 to 1.03) (Fig. 2F).”
Quote in the paperSubstantial claim - Findingown data
No HLA supertype was significantly associated with overall survival in NSCLC patients.
“We did not find any supertype significantly associated with overall survival in patients with NSCLC, likely because of the limited sample size.”
Quote in the paperSubstantial claim - Findingown data
In an exploratory analysis, homozygosity at HLA-DP was associated with reduced survival.
“As an exploratory analysis, we also found that HLA-II homozygosity at HLA-DP was associated with reduced survival (P = 0.018, HR = 1.45, 95% CI 1.06 to 2.00) (fig. S2A).”
Quote in the paperNot a substantial claim - Findingown data
The B44 survival association was influenced by HLA-B*18:01, HLA-B*44:02, HLA-B*44:03, HLA-B*44:05, and HLA-B*50:01.
“The B44 association was influenced by HLA-B*18:01, HLAB*44:02, HLA-B*44:03, HLA-B*44:05, and HLAB*50:01 (P = 0.001, HR = 0.49, 95% CI 0.32 to 0.76) (Fig. 2C and Table 1).”
Quote in the paperSubstantial claim - Findingown data
In molecular dynamics simulations, bound peptide expanded the binding cleft and broke the structural bridge in HLA-B*07:02 and HLA-B*53:01.
“In the case of HLA-B*07:02 and HLA-B*53:01, MD simulations demonstrated that the bound peptide expands the respective HLA binding cleft, effectively breaking the bridge (fig. S4, A to D).”
Quote in the paperSubstantial claim - Findingown data
Among HLA-B alleles with available crystal structures, HLA-B*15:01, HLA-B*07:02, and HLA-B*53:01 possess a structural bridge in the peptide-binding groove formed by Arg62, Ile66, and Leu163.
“Out of all the HLA-B alleles that were available for three-dimensional structural analysis [n = 119 Protein Data Bank (PDB) crystal structures] (table S9), we identified three alleles at their highest resolutions—HLAB*15:01, HLA-B*07:02, and HLA-B*53:01—as possessing a structural bridge in the peptide-binding groove (Arg62, Ile66, and Leu163) (Fig. 3, B and C).”
Quote in the paperSubstantial claim - Findingown data
Homozygosity at the HLA-DPB locus was associated with decreased survival.
“Additionally, homozygosity at the HLA-DPB locus was associated with decreased survival (P = 0.04, HR = 1.37, 95% CI 1.07 to 1.87).”
Quote in the paperNot a substantial claim - Findingown data
The number of somatic mutations in tumors did not differ significantly between HLA-I homozygous and heterozygous patients.
“The number of somatic mutations in tumors was not statistically different between homozygous and heterozygous patients (fig. S1, A and B).”
Quote in the paperSubstantial claim - Findingown data
The association between HLA-I homozygosity and reduced survival remained significant after adjusting for mutation load, tumor stage, age, and drug class in cohort 1 and cohort 2.
“Cox regression modeling when analyzed for mutation load, tumor stage, age, and drug class in cohort 1 (P = 0.02, HR = 1.50, 95% CI 1.07 to 2.10) (table S2) and in cohort 2 (P = 0.028, HR = 1.31, 95% CI 1.03 to 1.67) (table S3).”
Quote in the paperSubstantial claim - Findingown data
The combined effect of B44 alleles and mutation load on survival was greater than mutation burden alone.
“The combined effect of the B44 alleles and mutation load was greater than simply considering mutation burden alone (Fig. 2, G and H).”
Quote in the paperSubstantial claim - Premisecitation
Most B44 supertype members share a preference for peptides with glutamate at anchor position P2 and polar or hydrophobic residues at the C terminus.
“Most members of the B44 supertype share a preference for peptides with Glu (E) at anchor position P2 and polar and hydrophobic residues at the C terminus (Fig. 2J) (54, 56).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
HLA-I genes influence patient survival after immune checkpoint blockade.
“Our findings reveal that HLA-I genes influence patient survival to ICB.”
Quote in the paperSubstantial claim - Interpretationown data
The diversity of HLA molecules in a patient influences the selection and clonal expansion of T cells reactive against neoantigens after immune checkpoint blockade.
“Altogether, these results indicate that the diversity of HLA molecules in a given patient influences the selection and the resulting T cell clonal expansion reactive against neoantigens after ICB (51).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [51] Li B, Nat. Genet 48, 725– 732 (2016). 27240091 PMC5298896 source
Not checked in the free run.
- Premisecitation
The anti-tumor activity of immune checkpoint blockade depends on CD8+ T cell and HLA class I-dependent immune activity.
“The anti-tumor activity of ICB has been shown to depend on CD8+ T cell, HLA class I–dependent immune activity (34–36).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [34] Gubin MM, Nature 515, 577– 581 (2014). 25428507 PMC4279952 source
Not checked in the free run.
- cites [35] Tran E, Science 350, 1387– 1390 (2015). 26516200 PMC7445892 source
Not checked in the free run.
- cites [36] Tran E, N. Engl. J. Med 375, 2255– 2262 (2016). 27959684 PMC5178827 source
Not checked in the free run.
- Interpretationreasoning
The G > E enrichment suggests there may be enriched presentation of B44-restricted neoantigens.
“This observation suggests that there might be an enrichment of presentation of B44-restricted neoantigens.”
Quote in the paperNot a substantial claim - Premisecitation
An individual homozygous at at least one HLA-I locus is predicted to present a smaller, less diverse repertoire of tumor-derived neoantigens to cytotoxic T lymphocytes than a person heterozygous at each class I locus.
“As such, an individual homo-zygous in at least one HLA-I locus would be predicted to present a smaller, less diverse repertoire of tumor-derived neoantigens to cytotoxic T lymphocytes (CTLs) as compared with a person who is heterozygous at each class I locus (32).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [32] Doherty PC, Zinkernagel RM, Lancet 1, 1406– 1409 (1975). 49564 source
Not checked in the free run.
- Premisecitation
Only a small fraction of presented tumor mutations are immunogenic in cancer patients.
“Given that only a small fraction of presented tumor mutations are immunogenic in cancer patients (45, 46), our findings suggest that relatively small differences in the number of available HLA-I molecules in a given individual can present major challenges to effective antitumor T cell responses and efficacy to ICB.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
An explanation for the mutation-response correlation is that more tumor mutations presented on the cell surface increase the probability of neoantigen recognition by cytotoxic T cells.
“An explanation for this observation is that the number of tumor mutations presented on the cell surface increases the probability of neoantigen recognition by cytotoxic T cells (42).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42] Schumacher TN, Schreiber RD, Science 348, 69– 74 (2015). 25838375 source
Not checked in the free run.
- Interpretationown data
The survival advantage of HLA-I heterozygosity in immune checkpoint blockade-treated patients at both germline and somatic levels highlights its importance in the dynamic anti-tumor immune response and immune evasion.
“Furthermore, the demonstration of a significant survival advantage to HLA-I heterozygosity in patients treated with ICB both at the germline and somatic level highlights its importance in the dynamic anti-tumor immune response and immune evasion.”
Quote in the paperSubstantial claim - Interpretationreasoning
Small differences in the number of available HLA-I molecules in a patient can present major challenges to effective antitumor T cell responses and immune checkpoint blockade efficacy.
“our findings suggest that relatively small differences in the number of available HLA-I molecules in a given individual can present major challenges to effective antitumor T cell responses and efficacy to ICB.”
Quote in the paperSubstantial claim
- May combine two claims. 10
- Classified as probably not a substantial claim. 6
May combine two claims.
Findingown dataIn molecular dynamics simulations of HLA-B*15:01, the structural bridge was largely maintained with peptide present, and the bridging residues became much less flexible.
“Conversely, in the HLA-B*15:01 molecule the bridge was largely maintained with the peptide present, and the bridging residues were also made much less flexible (Fig. 3, D and E).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataNo particular gene mutation was associated with decreased overall survival.
“However, we did not find any particular gene mutation associated with decreased overall survival.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe mean bridge separation remained nearly constant at about 6 Å in both HLA-B*15:01 systems, but fluctuations were less dramatic in the peptide-bound complex.
“Although the mean bridge separation remained nearly constant (~6 Å) in both systems of HLAB*15:01 (Fig. 3E), the fluctuations in this distance were less dramatic in the peptide-bound complex.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBoth the B44 and B62 allele associations remained statistically significant after Bonferroni correction.
“Both of these B44 and B62 allele associations remained statistically significant (P = 0.01 and P = 0.02, respectively) after a Bonferroni correction.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAmong HLA-I loci, homozygosity at HLA-C was associated with reduced overall survival, and HLA-B homozygosity showed a similar trend.
“The effect of homozygosity on survival because of specific HLA-I locus seemed mostly associated with HLA-B (P = 0.052, HR = 1.66, 95% CI 0.93 to 2.94) (Fig. 1C) and HLA-C (P = 0.004, HR = 1.60, 95% CI 1.16 to 2.21) (Fig. 1C).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataBoth patient-specific HLA-I genotype and somatic HLA-I alterations affect clinical outcome to immune checkpoint blockade.
“Both patient-specific HLA-I genotype as well as somatic alterations in tumors affected clinical outcome to ICB, suggesting that these factors could be considered in the design of future clinical trials.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe presence of B44 is predictive of response to immune checkpoint blockade rather than prognostic.
“The B44 alleles did not associate with survival in patients with melanoma from The Cancer Genome Atlas (TCGA), suggesting that the presence of B44 was predictive of response to ICB and was not prognostic (Fig. 2I).”
Quote in the paperSubstantial claim- Rests on an assumption: The TCGA melanoma cohort is an appropriate untreated comparator for determining whether B44 is prognostic rather than predictive.
May combine two claims.
PremisecitationHLA-B is generally expressed at higher levels on the cell surface than HLA-A and HLA-C, and HLA-B alleles bind a greater diversity of peptides.
“Our findings may be explained because HLA-B is generally expressed at higher levels on the cell surface than HLA-A and HLA-C and because HLA-B alleles bind to a greater diversity of peptides (38, 39).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThe B pocket of HLA-A alleles binds broadly hydrophobic amino acids, whereas the B pocket of HLA-B alleles can accommodate a greater variety of residues.
“Amino acids that bind to the B pocket of HLA-A alleles are broadly hydrophobic. By contrast, the B pocket of HLA-B alleles can accommodate a greater variety of residues (29, 39).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAntigen-presenting cells express higher levels of HLA-C on the cell surface than other cell types, suggesting heterozygous HLA-C may facilitate continuous CTL priming.
“Antigen-presenting cells express higher levels of HLA-C on the cell surface than do other cell types (40), suggesting that heterozygous HLA-C may facilitate continuous CTL priming (41).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
Interpretationown dataHLA-I homozygosity and HLA-I loss of heterozygosity represent a genetic barrier to effective immunotherapy.
“Our findings indicate that HLA-I homozygosity and LOH at HLA-I represent a genetic barrier to effective immunotherapy, and alternative ways to harness the immune system may be necessary to maximize clinical benefit.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationThe total number of somatic coding mutations in a cancer genome correlates with response to immune checkpoint blockade.
“Previous reports have shown that the total number of somatic coding mutations in a cancer genome correlates with response to ICB (7, 8, 10–12, 17).”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [7] Hugo W, Cell 165, 35– 44 (2016). 26997480 PMC4808437 source
Not checked in the free run.
- cites [8] Le DT, N. Engl. J. Med 372, 2509– 2520 (2015). 26028255 PMC4481136 source
Not checked in the free run.
- cites [10] Rizvi NA, Science 348, 124– 128 (2015). 25765070 PMC4993154 source
Not checked in the free run.
- cites [11] Snyder A, N. Engl. J. Med 371, 2189– 2199 (2014). 25409260 PMC4315319 source
Not checked in the free run.
- cites [12] Van Allen EM, Science 350, 207– 211 (2015). 26359337 PMC5054517 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThese supertypes together cover most HLA-A and HLA-B alleles found in distinct populations.
“These supertypes together cover most HLA-A and HLA-B alleles found in distinct populations (52, 53).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationIndividual HLA-I alleles are classified into 12 discrete supertypes based on similar peptide-anchor-binding specificities.
“Individual HLA-I alleles are classified into 12 discrete supertypes (52, 53), on the basis of similar peptide-anchor–binding specificities (26, 52, 53).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMismatched HLA-DP is associated with graft-versus-host disease.
“Mismatched HLA-DP has been shown to be associated with graft-versus-host disease (47).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] Petersdorf EW, N. Engl. J. Med 373, 599– 609 (2015). 26267621 PMC4560117 source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationLoss of heterozygosity of HLA-I genes has been reported in cancer.
“Previous work has reported loss of heterozygosity (LOH) of HLA-I genes in cancer (43, 44).”
Quote in the paperSubstantial claim0 of 2 sources checked
The authors state this as an assumption.
Before this study, the extent to which a patient's HLA class I genotype affects response to anti-PD-1 or anti-CTLA-4 therapy was unknown.
“However, the extent to which patient-specific HLA-I genotype influences response to anti–programmed cell death protein 1 or anti–cytotoxic T lymphocyte–associated protein 4 is currently unknown.”
The paper relies on this without support.
The two study cohorts are representative of advanced cancer patients treated with immune checkpoint blockade, so the observed associations apply beyond these cohorts.
“We examined two sets of cancer patients (henceforth called cohort 1 and cohort 2) treated with ICB.”
The paper relies on this without support.
The TCGA melanoma cohort is an appropriate untreated comparator for determining whether B44 is prognostic rather than predictive.
“The B44 alleles did not associate with survival in patients with melanoma from The Cancer Genome Atlas (TCGA), suggesting that the presence of B44 was predictive of response to ICB and was not prognostic (Fig. 2I).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
HLA homozygosity is linked to decreased survival in cancer patients treated with immune checkpoint blockade.
“HLA homozygosity has been linked to decreased survival in cancer patients treated with ICB”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Chowell et al., 2018
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Univariate B44 result is called significant despite P = 0.054
MajorThe paper describes the cohort 2 univariate B44 result as significant, but its reported P value exceeds 0.05 and its 95% confidence interval includes the null hazard ratio of 1.
“had signif icantly better overall survival on univariate”
“(P = 0.054, HR = 0.32, 95% CI 0.09 to 1.1)”
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The Cellular Immunotherapy Revolution: Arming the Immune System for Precision Therapy
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Adverse events associated with immune checkpoint inhibitor treatment for cancer
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Phosphoinositide 3-kinase signaling can modulate MHC class I and II expression
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- Authors
- Chowell, D., Morris, L. G. T., Grigg, C. M., Weber, J. K., Samstein, R. M., Makarov, V., Kuo, F., Kendall, S. M., Requena, D., Riaz, N., Greenbaum, B., Carroll, J., Garon, E., Hyman, D. M., Zehir, A., Solit, D., Berger, M., Zhou, R., Rizvi, N. A., & Chan, T. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Columbia University Irving Medical Center (US)
- IBM Research - Thomas J. Watson Research Center (US)
- Rockefeller University (US)
- Tisch Cancer Institute (US)
- University of California, Los Angeles (US)
- Corresponding author
- Morris, Luc G. T.
- Grigg, Claud M.
- Rizvi, Naiyer A.
- Chan, Timothy A.
- ORCID
- Chowell, Diego
- Morris, Luc G. T.
- Grigg, Claud M.
- Weber, Jeffrey K.
- Samstein, Robert M.
- Makarov, Vladimir
- Kuo, Fengshen
- Kendall, Sviatoslav M.
- Requena, David
- Riaz, Nadeem
- Greenbaum, Benjamin
- Carroll, James
- Garon, Edward
- Hyman, David M.
- Zehir, Ahmet
- Solit, David
- Berger, Michael
- Zhou, Ruhong
- Rizvi, Naiyer A.
- Chan, Timothy A.
- Venue
- Science
- Published
- 2018-02-02
- Volume
- 359
- Issue
- 6375
- Pages
- 582-587
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC6057471
- OpenAlex
- W2774712455
- Semantic Scholar
- 69554fde1077dd3ec7ca8ee3e5bf91339d79a7d4
- Cited by
- 1,142
- References
- 87
- Citations by year
- 2026: 91 · 2025: 103 · 2024: 123 · 2023: 151 · 2022: 163 · 2021: 158 · 2020: 171 · 2019: 120 · 2018: 59 · 2017: 2 · 2015: 1
- FWCI
- 42.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- NIH (1R01CA205426)
- Starr Cancer Consortium
- Pershing Square Sohn Cancer Research Alliance
- NIH/NCI Cancer Center Support Grant (P30 CA008748)
- Stand Up 2 Cancer
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- HLA class I, HLA heterozygosity, HLA homozygosity, cancer immunotherapy, immune checkpoint inhibitors, CD8+ T cells
- MeSH terms
- Adult, Aged, Antigens, Neoplasm, Genetic Carrier Screening, Humans, Immunotherapy, Melanoma, Middle Aged, Protein Conformation, Skin Neoplasms, Cohort Studies, Histocompatibility Antigens Class I, Treatment Outcome, Antigen Presentation, CD8-Positive T-Lymphocytes, Cancer Vaccines, Young Adult, CTLA-4 Antigen, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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