# Human Leukocyte Antigen (HLA) and Tumor Immunity: A Critical Link in Cancer Immunotherapy

**Authors:** Donath Damian

PMC · DOI: 10.1002/iid3.70363 · 2026-02-16

## TL;DR

This review explains how HLA molecules influence cancer immunity and could lead to better immunotherapies.

## Contribution

The paper highlights new insights into HLA's role in tumor immunity and potential for HLA-based cancer treatments.

## Key findings

- HLA polymorphisms and expression patterns are closely linked to tumor progression and immune modulation.
- HLA molecules can either enhance or suppress antitumor immune responses.
- Understanding HLA-tumor interactions may improve cancer immunotherapy outcomes.

## Abstract

Malignant tumors pose a serious threat to human health and survival, with profound economic consequences worldwide. Human leukocyte antigens (HLAs), encoded by the human major histocompatibility complex, represent one of the most polymorphic genetic systems and play a vital role in immune regulation. This review summarizes the structural and functional characteristics of HLA molecules, their polymorphism and expression in tumor tissues, their involvement in tumor progression and immune responses, and their emerging applications in tumor immunotherapy.

A thorough literature review was conducted focusing on HLA molecules, their genetic variability in tumor tissues, and their impact on tumor immunity and cellular proliferation. The potential clinical utility of targeting HLA molecules in tumor immunotherapy was also evaluated.

HLA polymorphisms and expression patterns have been closely associated with tumor initiation, progression, and immune modulation. These molecules influence tumor cell growth and regulate antitumor immune responses, either enhancing or suppressing immunity. HLA molecules are therefore critical in shaping the immune system's capacity to detect and eliminate cancer cells.

This review underscores the pivotal role of HLA molecules in cancer immunology. A deeper understanding of HLA‐tumor interactions offers promising avenues for the development of HLA‐based immunotherapies, potentially improving clinical outcomes in cancer treatment.

## Linked entities

- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, LTA (lymphotoxin alpha) [NCBI Gene 4049] {aka LT, TNFB, TNFSF1, TNLG1E}, HLA-DPB1 (major histocompatibility complex, class II, DP beta 1) [NCBI Gene 3115] {aka DPB1, HLA-DP, HLA-DP1B, HLA-DPB}, LILRB1 (leukocyte immunoglobulin like receptor B1) [NCBI Gene 10859] {aka CD85J, ILT-2, ILT2, LIR-1, LIR1, MIR-7}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, LILRB2 (leukocyte immunoglobulin like receptor B2) [NCBI Gene 10288] {aka CD85D, ILT-4, ILT4, LIR-2, LIR2, MIR-10}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, HLA-G (major histocompatibility complex, class I, G) [NCBI Gene 3135] {aka MHC-G}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, TNFRSF25 (TNF receptor superfamily member 25) [NCBI Gene 8718] {aka APO-3, DDR3, DR3, LARD, TNFRSF12, TR3}, KLRD1 (killer cell lectin like receptor D1) [NCBI Gene 3824] {aka CD94}, HLA-DMA (major histocompatibility complex, class II, DM alpha) [NCBI Gene 3108] {aka D6S222E, DMA, HLADM, RING6}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TAP2 (transporter 2, ATP binding cassette subfamily B member) [NCBI Gene 6891] {aka ABC18, ABCB3, APT2, D6S217E, MHC1D2, PSF-2}, HLA-S (major histocompatibility complex, class I, S (pseudogene)) [NCBI Gene 267015] {aka HLA-17}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, PSMB8 (proteasome 20S subunit beta 8) [NCBI Gene 5696] {aka ALDD, D6S216, D6S216E, JMP, LMP7, NKJO}, HLA-B (major histocompatibility complex, class I, B) [NCBI Gene 3106] {aka AS, B-4901, HLAB}, HLA-E (major histocompatibility complex, class I, E) [NCBI Gene 3133] {aka HLA-6.2, QA1}, HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) [NCBI Gene 3119] {aka CELIAC1, HLA-DQB, IDDM1}, HLA-DQA1 (major histocompatibility complex, class II, DQ alpha 1) [NCBI Gene 3117] {aka CELIAC1, DQ-A1, DQA1, HLA-DQA, HLA-DQA1*}, KLRC1 (killer cell lectin like receptor C1) [NCBI Gene 3821] {aka CD159A, NKG2, NKG2A}, TAP1 (transporter 1, ATP binding cassette subfamily B member) [NCBI Gene 6890] {aka ABC17, ABCB2, APT1, D6S114E, MHC1D1, PSF-1}, HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123] {aka DRB1, HLA-DR1B, HLA-DRB, SS1}, EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, EZH1 (enhancer of zeste 1 polycomb repressive complex 2 subunit) [NCBI Gene 2145] {aka KMT6B}, MICA (MHC class I polypeptide-related sequence A) [NCBI Gene 100507436] {aka MIC-A, PERB11.1}, B2M (beta-2-microglobulin) [NCBI Gene 567] {aka AMYLD6, IMD43, MHC1D4}, HLA-F (major histocompatibility complex, class I, F) [NCBI Gene 3134] {aka CDA12, HLA-5.4, HLA-CDA12, HLAF}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CXCL14 (C-X-C motif chemokine ligand 14) [NCBI Gene 9547] {aka BMAC, BRAK, KEC, KS1, MIP-2g, MIP2G}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, KLRC2 (killer cell lectin like receptor C2) [NCBI Gene 3822] {aka CD159c, NKG2-C, NKG2C}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, PSMB9 (proteasome 20S subunit beta 9) [NCBI Gene 5698] {aka LMP2, PRAAS3, PRAAS6, PSMB6i, RING12, beta1i}
- **Diseases:** chronic (MESH:D002908), esophageal cancer (MESH:D004938), HCC (MESH:D006528), liver conditions (MESH:D017093), ovarian cancer (MESH:D010051), breast and colon cancers (MESH:D001943), lymph node (MESH:D000072717), infected (MESH:D007239), leukemia (MESH:D007938), colorectal cancer (MESH:D015179), endometrial cancer (MESH:D016889), metastasis (MESH:D009362), hypoxia (MESH:D000860), cervicitis (MESH:D002575), Kaposi's sarcoma (MESH:D012514), squamous cell carcinoma (MESH:D002294), head and neck squamous cell carcinoma (MESH:D000077195), NSCLC (MESH:D002289), renal cancer (MESH:D007680), HPV infection (MESH:D030361), ankylosing spondylitis (MESH:D013167), cholangiocarcinoma (MESH:D018281), Hodgkin's lymphoma (MESH:D006689), autoimmune and (MESH:D001327), gastric cancer (MESH:D013274), febrile (MESH:D000071072), Behcet's disease (MESH:D001528), GVHD (MESH:D006086), CIN (MESH:D002578), pre-eclampsia (MESH:D011225), CML (MESH:D015464), Malignant tumors (MESH:D009369), lung cancer (MESH:D008175), cervical cancer (MESH:D002583), glioma (MESH:D005910), melanoma (MESH:D008545), pancreatic ductal adenocarcinoma (MESH:D021441), terminal liver disease (MESH:D008107), inflammation (MESH:D007249)
- **Chemicals:** ruxolitinib (MESH:C540383)
- **Species:** Human papillomavirus 16 (serotype) [taxon 333760], Homo sapiens (human, species) [taxon 9606], hepatitis C virus [taxon 11103]
- **Mutations:** G-308A
- **Cell lines:** SKOV3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909283/full.md

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Source: https://tomesphere.com/paper/PMC12909283