Table 1.

HLA class I– and class II–restricted tumor-specific unique antigens recognized by T cells on single human cancers

TumorT-cell originGene name by HUGO Gene Nomenclature CommitteeBiological function of the normal proteinHLA allelePeptide*Mechanism of generationWild-type alleleReference
MelanomaTILcatenin (cadherin-associated protein), β1Cell-cell adhesionA24SYLDSGIHF (S)MutationPresent10
Wnt signalingHLA anchor
MelanomaPBLcyclin-dependent kinase 4 §Cell cycleA2ACDPHSGHFV (R)MutationPresent11
HLA anchor
MelanomaTILhedgehog acyltransferaseHedgehog signalingA1FLEGNEVGKTY (G)MutationPresent12
HLA anchor
MelanomaPBLmelanoma associated (mutated) antigen-1§UnknownB44EEKLIVVLF (S)MutationPresent8
contract contact
MelanomaPBLmelanoma associated (mutated) antigen-2§Protein transportB44SELFRSGLDSY (R)MutationPresent13
TCR contact
C6FRSGLDSYV (R)Mutation
TCR contact
MelanomaPBLmelanoma associated (mutated) antigen-3§Nucleic acid metabolismA68EAFIQPITR (S)MutationPresent14
HLA anchor
MelanomaTILmyosin class ICellular motilityA3KINKNPKYK (E)MutationPresent15
TCR contact
MelanomaPBLperoxiredoxin 5Oxidative stressA2LLLDDLLVSI (S)MutationAbsent16
TCR contact
MelanomaPBLOS-9Regulation of hypoxic responsesB44KELEGILLL (P)MutationAbsent17
MelanomaTILmajor histocompatibility complex, class I, A11Histocompatibiliy antigen18
MelanomaTILgrowth arrest-specific 7Cell cycleA2SLADEAEVYL (H)MutationPresent19
LADEAEVYL (H)
MelanomaTILglyceraldehyde 3-phosphate dehydrogenaseEnergy metabolismA2GIVEGLITTV (M)MutationPresent19
GIVEGLITT (M)
MelanomaPBLsirtuin-2§Transcriptional silencingA3KIFSEVTLK (P)MutationPresent20
MelanomaPBLglycoprotein (transmembrane) nmb§Melanosomal proteinA3TLDWLLQTPK (G)MutationPresent20
MelanomaPBLelongation factor Tu GTP binding domain containing 2§RNA processingA3TLDWLLQTPK (G)MutationPresent20
MelanomaPBLzinc finger, UBR1 type 1§Cell cycleA3TLDWLLQTPK (G)MutationPresent20
MelanomaPBLsmall nuclear ribonucleoprotein D1 polypeptide 16 kDa§RNA processingA3TLDWLLQTPK (G)MutationPresent20
MelanomaTILprotein tyrosine phosphatase, receptor type, K§Cell-cell adhesionA3TLDWLLQTPK (G)MutationPresent20
MelanomaTILneo-poly(A) polymeraseRNA processingA3TLDWLLQTPK (G)MutationPresent20
MelanomaTILfibronectinExtracellular matrix componentA3TLDWLLQTPK (G)MutationPresent20
MelanomaTILlow-density lipoprotein receptor/fucosyltransferase 4A3TLDWLLQTPK (G)MutationPresent20
MelanomaTILtriosephosphate isomerase 1Energy metabolismDR1GELIGILNAAKVPAD (T)MutationPresent25
TCR contact
MelanomaTILcell division cycle 27Cell cycleDR4Indirect effectcMutation26
MelanomaPBLantigen recognized by Treg cells-1**UnknownDR1Indirect effectcMutationAbsent27
Head and neck squamous cell carcinomaPBLcaspase 8, apoptosis-related cysteine peptidaseApoptosisB35Indirect effectcMutationPresent28
Lung non–small-cell carcinomaPBLeukaryotic translation elongation factor 2Protein translationA68ETVSEQSNV (G)MutationPresent29
TCR contact
Lung non–small-cell carcinomaTILactinin, α4§AdhesionA2FIASNGVKLV (K)Mutation30
TCR contact
Lung non–small-cell carcinomaPBLmalic enzyme§Energy metabolismA2FLDEFMEGV (A)MutationAbsent31
Lung non–small-cell carcinomaTDLnuclear transcription factor Y, γTranscriptional activatorB52AQQITKTEV (Q)MutationAbsent32
Bladder carcinomaPBLlysophosphatidylglycerol acyltransferase 1Phospholipids biosynthesisB44AEPINIQTW (D)MutationPresent33
Renal cell carcinomaPBLmajor histocompatibility complex, class I, A2Histocompatibility antigen-Mutation34
Renal cell carcinomaPBLintegrator complex subunit 1pre-mRNA processingA1QTACEVLDY (T)MutationPresent35
Renal cell carcinomaTILheat shock 70-kDa protein 1BHeat shock proteinA2SLFEGIDIYT (F)MutationPresent36
TCR contact
Colorectal carcinomaPBLcolorectal tumor-associated antigen-1UnknownDR4, DR13Indirect effectcMutationPresent37
  • Abbreviations: TIL, tumor-infiltrating lymphocytes; PBL, peripheral blood lymphocytes; TDL, tumor draining lymph nodes.

  • * Bold residues in the epitope indicate the mutation. The wild-type residue is shown in brackets. The mutations may create a novel HLA anchor residue or a TCR contact residue.

  • Antigens encoded by genes of which the alteration, although rare, can be shared by more than one tumor.

  • Antigens recognized by TIL able to mediate tumor regression following adoptive transfer.

  • § Antigens recognized by T cells isolated from long-term survivors.

  • Antigens recognized by T cells of a single patient: melanoma-associated (mutated) antigen-1, -2, -3 identified by T cells from patient LB33; growth arrest-specific 7 and glyceraldehyde 3-phosphate dehydrogenase identified by T cells from patient 2098; sirtuin-2, glycoprotein (transmembrane) nmb, elongation factor Tu GTP binding domain containing 2, zinc finger UBR1 type 1, and small nuclear ribonucleoprotein D1 polypeptide 16 kDa identified by T cells from patient DT.

  • For these antigens, the mutation was not contained within the sequence of the antigenic peptide, but had an indirect effect involving antigen processing (22), relocalization (26), or generation of new proteins (27, 28).

  • ** This antigen was recognized by HLA class II–restricted CD4+ CD25+ regulatory T cells.