Immune Modulation Through KIR–HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer
Abstract
1. Introduction
2. Results
2.1. Baseline Patient Characteristics and Clinical Outcome
2.2. Frequencies of KIR Genes and Their Ligands
2.3. Frequency of KIR–Ligand Combinations
2.4. Frequency of KIR Genotypes and Haplotypes
2.5. Survival Analysis According to KIR Genes or Their Ligands
2.6. Survival Analysis According to KIR–Ligand Combinations
2.7. Survival Analysis According to KIR Haplotypes
2.8. Survival Analysis According to Centromeric–Telomeric KIR Haplotypes
2.9. Univariate and Multivariate Analyses
3. Discussion
4. Materials and Methods
4.1. Patients and Inclusion Criteria
4.2. Ethical Considerations
4.3. Sample Processing and DNA Isolation for Genotyping
4.4. KIR Genotyping
4.5. HLA Genotyping
4.6. KIR–HLA Interactions
4.7. Statistical Analysis
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | KRAS-WT (n = 55) (%) | KRAS-Mutant (n = 69) (%) |
---|---|---|
Gender (n, %) | Male: 39 (70.9) Female: 16 (29.1) | Male: 35 (50.7) Female: 34 (49.3) |
Age (median, range) | 64 (41–84) | 64 (42–82) |
ECOG (n, %) | 0: 24 (43.6) 1: 22 (40) 2: 3 (5.5) Unknown: 6 (10.9) | 0: 12 (17.4) 1: 51 (73.9) 2: 6 (8.7) |
Primary site (n, %) | Right colon: 16 (29.1) Left colon: 21 (38.2) Rectum: 18 (32.7) | Right colon: 16 (23.2) Left colon: 35 (50.7) Rectum: 18 (26.1) |
Laterality (n, %) | Right-sided: 16 (29.1) Left-sided: 39 (70.9) | Right-sided: 16 (23.2) Left-sided: 53 (76.8) |
Number of metastatic sites (n, %) | 1: 28 (50.9) 2: 19 (34.5) 3 or more: 8 (14.5) | 1: 26 (37.7) 2: 27 (39.1) 3 or more: 16 (23.2) |
Previous treatments (n, %) | Yes: 30 (54.5) No: 24 (43.6) Unknown: 1 (1.8) | Yes: 69 (100) No: 0 (0) |
Treatment time, months (median, range) | 8.1 (1.9–12) | 2 (0.5–12) |
Number of treatment cycles (median, range) | 17 (3–24) | 4 (1–24) |
Reason for end of treatment (n, %) | Progression: 28 (73.7) Death: 1 (2.6) Toxicity: 1 (2.6) Other: 8 (21.1) | Progression: 59 (86.8) Death: 2 (2.9) Toxicity: 4 (5.9) Other: 3 (4.4) |
Progression at 12 months (n, %) | Yes: 33 (60) No: 22 (40) | Yes: 68 (92.8) No: 1 (1.4) |
Exit at 12 months (n, %) | Yes: 14 (25.5) No: 41 (74.5) | Yes: 51 (73.9) No: 18 (26.1) |
Exit reason (n, %) | Progression: 8 (57.2) Adverse event: 1 (7.1) Unknown: 5 (35.7) | Progression: 42 (82.4) Adverse event: 2 (3.9) Unknown: 7 (13.7) |
KIR Genes and HLA Ligands | KRAS-WT (n = 55) (%) | KRAS-Mutant (n = 69) (%) | p-Value (X2/Fisher) | |
---|---|---|---|---|
KIR gene | ||||
2DL1 (n, %) | Positive: 54 (98.2) Negative: 1 (1.8) | Positive: 63 (91.3) Negative: 6 (8.7) | 0.131 | (Fisher) |
2DL2 (n, %) | Positive: 31 (56.4) Negative: 24 (43.6) | Positive: 37 (53.6) Negative: 32 (46.4) | 0.761 | (X2) |
2DL3 (n, %) | Positive: 53 (96.4) Negative: 2 (3.6) | Positive: 62 (89.9) Negative: 7 (10.1) | 0.296 | (Fisher) |
2DL5 (n, %) | Positive: 32 (58.2) Negative: 23 (41.8) | Positive: 39 (56.5) Negative: 30 (43.5) | 0.853 | (X2) |
3DL1 (n, %) | Positive: 50 (90.9) Negative: 5 (9.1) | Positive: 62 (89.9) Negative: 7 (10.1) | 0.844 | (X2) |
2DS1 (n, %) | Positive: 25 (45.5) Negative: 30 (54.5) | Positive: 37 (53.6) Negative: 32 (46.4) | 0.366 | (X2) |
2DS2 (n, %) | Positive: 31 (56.4) Negative: 24 (43.6) | Positive: 36 (52.2) Negative: 33 (47.8) | 0.642 | (X2) |
2DS3 (n, %) | Positive: 19 (34.5) Negative: 36 (65.5) | Positive: 29 (42) Negative: 39 (56.5) Unknown: 1 (1.4) | 0.440 | (X2) |
2DS4 (n, %) | Positive: 50 (90.9) Negative: 5 (9.1) | Positive: 63 (91.3) Negative: 6 (8.7) | 1.000 | (Fisher) |
2DS5 (n, %) | Positive: 19 (34.5) Negative: 36 (65.5) | Positive: 23 (33.3) Negative: 46 (66.7) | 0.887 | (X2) |
3DS1 (n, %) | Positive: 25 (45.5) Negative: 30 (54.5) | Positive: 27 (39.1) Negative: 42 (60.9) | 0.478 | (X2) |
2DP1 (n, %) | Positive: 54 (98.2) Negative: 1 (1.8) | Positive: 62 (89.9) Negative: 7 (10.1) | 0.075 | (Fisher) |
HLA ligand | ||||
Bw4 (n, %) | Positive: 46 (83.6) Negative: 9 (16.4) | Positive: 46 (66.7) Negative: 21 (31.4) | 0.056 | (X2) |
C1 (n, %) | Positive: 45 (81.8) Negative: 10 (18.2) | Positive: 54 (80.6) Negative: 13 (19.4) | 0.864 | (X2) |
C2 (n, %) | Positive: 37 (67.3) Negative: 18 (32.7) | Positive: 48 (71.6) Negative: 19 (28.4) | 0.601 | (X2) |
KIR–Ligand Combinations | KRAS-WT n (%) | KRAS-Mutant n (%) | p-Value (X2) |
---|---|---|---|
3DL1–Bw4 | Positive: 41 (82) Negative: 9 (18) | Positive: 41 (68.3) Negative: 19 (31.7) | 0.101 |
2DL1–C2 | Positive: 36 (66.7) Negative: 18 (33.3) | Positive: 43 (69.4) Negative: 19 (30.6) | 0.757 |
2DL2–C1 | Positive: 26 (83.9) Negative: 5 (16.1) | Positive: 27 (75) Negative: 9 (25) | 0.373 |
2DL3–C1 | Positive: 44 (83) Negative: 9 (17) | Positive: 50 (82) Negative: 11 (18) | 0.883 |
2DS1–C2 | Positive: 17 (68) Negative: 8 (32) | Positive: 26 (72.2) Negative: 10 (27.8) | 0.722 |
3DS1–Bw4 | Positive: 20 (80) Negative: 5 (20) | Positive: 16 (59.3) Negative: 11 (40.7) | 0.105 |
Genotypes and Haplotypes | KRAS-WT n (%) | KRAS-Mutant n (%) | p-Value (X2) |
---|---|---|---|
AA | Positive: 12 (21.8) Negative: 43 (78.2) | Positive: 16 (26.2) Negative: 45 (73.8) | 0.579 |
AB | Positive: 30 (54.5) Negative: 25 (45.5) | Positive: 27 (44.3) Negative: 34 (55.7) | 0.269 |
BB | Positive: 13 (23.6) Negative: 42 (76.4) | Positive: 18 (29.5) Negative: 43 (70.5) | 0.475 |
CENA/TELA | Positive: 12 (21.8) Negative: 43 (78.2) | Positive: 16 (26.2) Negative: 45 (73.8) | 0.579 |
CENA/TELB | Positive: 12 (21.8) Negative: 43 (78.2) | Positive: 12 (19.7) Negative: 49 (80.3) | 0.776 |
CENB/TELA | Positive: 18 (32.7) Negative: 37 (67.3) | Positive: 14 (23) Negative: 47 (77) | 0.239 |
CENB/TELB | Positive: 13 (23.6) Negative: 42 (76.4) | Positive: 19 (31.1) Negative: 42 (68.9) | 0.366 |
KRAS-WT | KRAS-Mutant | |||
---|---|---|---|---|
PFS12 (IC 95%) | p-Value (Log Rank) | PFS12 (IC 95%) | p-Value (Log Rank) | |
2DS1 | Positive (25): 10.15 (8.11–12.19) Negative (30): 8.84 (5.56–12.12) | 0.955 | Positive (37): 1.84 (1.81–1) Negative (32): 1.84 (1.7–1.98) | 0.890 |
2DS2 | Positive (31): 8.71 (7.33–10.1) Negative (24): 8.43 (7.02–0.83) | 0.444 | Positive (36): 1.84 (1.62–2.07) Negative (33): 1.84 (1.79–1.89) | 0.163 |
2DS3 | Positive (19): 9.44 (7.96–10.92) Negative (36): 8.14 (6.88–9.42) | 0.314 | Positive (29): 1.83 (1.78–1.89) Negative (39): 1.84 (1.81–1.87) | 0.273 |
2DS4 | Positive (50): 8.34 (7.28–9.40) Negative (5): 11.06 (10.03–12.08) | 0.276 | Positive (63): 1.84 (1.81–1.87) Negative (6): 1.84 (0.85–2.83) | 0.800 |
2DS5 | Positive (19): 10.15 (7.72–12.58) Negative (36): 8.84 (6.21–11.47) | 0.751 | Positive (23): 1.84 (1.81–1.87) Negative (46): 1.84 (1.75–1.93) | 0.498 |
3DS1 | Positive (25): 10.15 (8.11–12.19) Negative (30): 8.84 (5.56–12.12) | 0.955 | Positive (27): 1.84 (1.81–1.87) Negative (42): 1.84 (1.72–1.96) | 0.968 |
2DL1 | Positive (54): 10.15 (7.58–12.72) Negative (1): 3.02 (0–3.02) | 0.031 | Positive (63): 1.84 (1.81–1.87) Negative (6): 2.04 (0.78–3.29) | 0.727 |
2DL2 | Positive (31): 8.71 (7.33–10.1) Negative (24): 8.43 (7.03–9.83) | 0.444 | Positive (37): 1.84 (1.61–2.07) Negative (32): 1.84 (1.79–1.89) | 0.232 |
2DL3 | Positive (53): 10.15 (8.09–12.22) Negative (2): 3.02 (1.29–13.73) | 0.944 | Positive (62): 1.84 (1.81–1.87) Negative (7): 2.04 (0.86–3.22) | 0.585 |
2DL5 | Positive (32): 10.15 (8.42–11.88) Negative (23): 8.84 (5.01–12.67) | 0.816 | Positive (39): 1.84 (1.61–2.07) Negative (30): 1.84 (1.77–1.91) | 0.032 |
3DL1 | Positive (50): 8.34 (7.28–9.40) Negative (5): 11.06 (10.03–12.84) | 0.276 | Positive (62): 1.84 (1.81–1.87) Negative (7): 1.84 (1.75–1.92) | 0.946 |
2DP1 | Positive (54): 10.15 (7.58–12.72) Negative (1): 3.02 (0–3.02) | 0.031 | Positive (62): 1.84 (1.81–1.87) Negative (7): 2.04 (0.86–3.22) | 0.976 |
Bw4 | Positive (46): 8.85 (7.81–9.91) Negative (9): 7.23 (4.6–9.85) | 0.064 | Positive (46): 1.84 (1.78–1.89) Negative (21): 1.84 (1.6–2.04) | 0.620 |
C1 | Positive (45): 9.96 (7.62–12.29) Negative (10): 10.42 (7.34–13.49) | 0.826 | Positive (54): 1.84 (1.79–1.89) Negative (13): 1.84 (1.69–1.99) | 0.198 |
C2 | Positive (37): 10.58 (9.07–12.09) Negative (18): 4.79 (0–12.17) | 0.219 | Positive (48): 1.84 (1.75–1.94) Negative (19): 1.81 (1.75–1.86) | 0.935 |
KRAS-WT | KRAS-Mutant | |||
---|---|---|---|---|
PFS12 (IC 95%) | p-Value (Log Rank) | PFS12 (IC 95%) | p-Value (Log Rank) | |
CENA/TELA Other | (n = 12) 8.81 (8.64–8.97) (n = 43) 10.42 (8.22–12.61) | 0.571 | (n = 16) 1.74 (1.61–1.87) (n = 45) 1.84 (1.74–1.94) | 0.011 |
CENA/TELA + CENB/TELB CENA/TELB + CENB/TELA | (n = 25) 10.15 (6.68–13.63) (n = 30) 9.96 (6.56–13.35) | 0.919 | (n = 35) 1.74 (1.51–1.97) (n = 26) 2.04 (1.74–2.33) | 0.002 |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Variable | Frequency | HR (95% CI) | p-Value | Frequency | HR (95% CI) | p-Value |
Gender | ||||||
Female | 16 (29.1%) | 1 | 0.877 | 16 (29.1%) | 1 | 0.682 |
Male | 39 (70.9%) | 0.94 (0.45–1.97) | 39 (70.9%) | 1.18 (0.54–2.58) | ||
Median Age | ||||||
<64 years | 25 (45.5%) | 1 | 0.788 | 25 (45.5%) | 1 | 0.477 |
>64 years | 30 (54.5%) | 0.91 (0.46–1.81) | 30 (54.5%) | 0.12 (0.04–0.37) | ||
ECOG | ||||||
0 | 24 (43.6%) | 1 | - | - | - | |
1 | 22 (40%) | 0.56 (0.17–1.19) | 0.136 | - | - | - |
2 | 3 (5.5%) | 0.46 (0.06–3.47) | 0.453 | - | - | - |
Number of cycles | ||||||
<6 | 5 (9.1%) | 1 | 0 | 5 (9.1%) | 1 | 0 |
>6 | 50 (90.9%) | 0.16 (0.06–0.43) | 50 (90.9%) | 0.13 (0.04–0.39) | ||
Laterality | ||||||
Right-sided | 16 (29.1%) | 1 | 0.849 | - | - | - |
Left-sided | 39 (70.9%) | 1.07 (0.51–2.26) | - | - | - | |
Number of Metastatic sites | ||||||
1 | 28 (50.9%) | 1 | 0.844 0.837 | - | - | - |
2 | 19 (34.5%) | 1.08 (0.51–2.28) | - | - | - | |
>3 | 8 (14.5%) | 1.11 (0.41–3.04) | - | - | - | |
KIR2DL1 | ||||||
No | 1 (1.8%) | 1 | 0.065 | - | - | - |
Yes | 54 (98.2%) | 0.14 (0.02–1.97) | - | - | - | |
KIR2DL2 | ||||||
No | 24 (43.6%) | 1 | 0.446 | - | - | - |
Yes | 31 (56.4%) | 0.77 (0.38–1.52) | - | - | - | |
KIR2DL3 | ||||||
No | 2 (3.6%) | 1 | 0.944 | - | - | - |
Yes | 53 (96.4%) | 1.07 (0.15–7.87) | - | - | - | |
KIR2DL5 | ||||||
No | 23 (41.8%) | 1 | 0.816 | - | - | - |
Yes | 32 (58.2%) | 0.92 (0.46–1.84) | - | - | - | |
KIR 2DS1 | ||||||
No | 30 (54.5%) | 1 | 0.955 | - | - | - |
Yes | 25 (45.5%) | 0.98 (0.49–1.95) | - | - | - | |
KIR 2DS2 | ||||||
No | 24 (43.6%) | 1 | 0.446 | - | - | - |
Yes | 31 (56.4%) | 0.77 (0.39–1.52) | - | - | - | |
KIR 2DS3 | ||||||
No | 36 (65.5%) | 1 | 0.317 | - | - | - |
Yes | 19 (34.5%) | 0.68 (0.33–1.44) | - | - | - | |
KIR 2DS4 | ||||||
No | 5 (9.1%) | 1 | 0.289 | - | - | - |
Yes | 50 (90.9%) | 2.17 (0.52–9.08) | - | - | - | |
KIR 2DS5 | ||||||
No | 36 (65.5%) | 1 | 0.751 | - | - | - |
Yes | 19 (34.5%) | 0.89 (0.43–1.84) | - | - | - | |
KIR 3DL1 | ||||||
No | 5 (9.1%) | 1 | 0.289 | - | - | - |
Yes | 50 (90.1%) | 2.17 (0.52–9.08) | - | - | - | |
KIR 3DS1 | ||||||
No | 30 (54.5%) | 1 | 0.955 | - | - | - |
Yes | 25 (45.5%) | 0.98 (0.49–1.95) | - | - | - | |
KIR 2DP1 | ||||||
No | 1 (1.8%) | 1 | 0.065 | - | - | - |
Yes | 54 (98.2%) | 0.14 (0.017–1.13) | - | - | - | |
- | - | - | ||||
KIR3DS1–Bw4 | ||||||
No | 5 (20%) | 1 | 0.026 | 5 (20%) | 1 | 0.033 |
Yes | 20 (80%) | 0.29 (0.1–0.86) | 20 (80%) | 0.49 (0.25–0.94) | ||
3DS1–HLAB | ||||||
Heterozygous (w4w6) | 15 (27.3%) | 1 | 0.019 | - | 1 | 0.013 |
Homozygous (w4w4 or w6w6) | 10 (18.2%) | 3.48 (1.23–9.86) | - | 2.22 (1.19–4.16) | ||
Genotype | ||||||
AB | 30 (54.5%) | 1 | - | - | - | |
AA | 12 (21.8%) | 1.9 (0.81–4.48) | 0.143 | - | - | - |
BB | 13 (23.6%) | 0.92 (0.38–2.23) | 0.849 | - | - | - |
Genotype | ||||||
AB | 30 (54.5%) | 1 | 0.517 | - | - | - |
AA or BB | 25 (45.4%) | 1.26 (0.62–2.56) | - | - | - | |
Semi-haplotype | ||||||
CENA/TELB or CENB/TELA | 30 (54.5%) | 1 | 0.108 | - | - | - |
CENA/TELA | 12 (21.8%) | 1.95 (0.86–4.41) | - | - |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Variable | Frequency | HR (95% CI) | p-Value | Frequency | HR (95% CI) | p-Value |
Gender | ||||||
Female | 34 (49.3%) | 1 | 0.629 | 34 (49.3%) | 1 | 0.71 |
Male | 35 (50.7%) | 0.89 (0.55–1.44) | 35 (50.7%) | 1.11 (0.65–1.88) | ||
Median Age | ||||||
<64 years | 33 (47.8%) | 1 | 0.178 | 33 (47.8%) | 1 | 0.47 |
>64 years | 36 (52.2%) | 1.41 (0.85–2.34) | 36 (52.2%) | 1.01 (0.98–1.04) | ||
ECOG | ||||||
0 | 12 (17.4%) | 1 | - | - | - | |
1 | 51 (73.9%) | 1.09 (0.58–2.05) | 0.792 | - | - | - |
2 | 6 (8.7%) | 1.26 (0.46–3.47) | 0.660 | - | - | - |
Number of cycles | ||||||
<6 | 55 (79.7%) | 1 | 0 | - | - | - |
>6 | 14 (20.3%) | 0.24 (0.12–0.45) | - | - | ||
Laterality | ||||||
Right-sided | 16 (23.2%) | 1 | 0.71 | - | - | - |
Left-sided | 53 (76.8%) | 1.11 (0.63–1.97) | - | - | - | |
Number of Metastatic sites | ||||||
1 | 28 (50.9%) | 1 | 0.38 0.09 | 28 (50.9%) | 1 | 0.47 0.002 |
2 | 19 (34.5%) | 1.28 (0.74–2.22) | 19 (34.5%) | 1.27 (0.67–2.40) | ||
>3 | 8 (14.5%) | 1.75 (0.91–3.37) | 8 (14.5%) | 2.94 (1.46–5.92) | ||
KIR2DL1 | ||||||
No | 6 (8.7%) | 1 | 0.736 | - | - | - |
Yes | 63 (91.3%) | 1.16 (0.49–2.69) | - | - | - | |
KIR2DL2 | ||||||
No | 32 (46.4%) | 1 | 0.247 | - | - | - |
Yes | 37 (53.6%) | 0.75 (0.46–1.22) | - | - | - | |
KIR2DL3 | ||||||
No | 7 (10.1%) | 1 | 0.598 | - | - | - |
Yes | 62 (89.9%) | 1.24 (0.56–2.74) | - | - | - | |
KIR2DL5 | ||||||
No | 30 (43.5%) | 1 | 0.039 | - | - | - |
Yes | 39 (56.5%) | 0.59 (0.35–0.97) | - | - | - | |
KIR2DS1 | ||||||
No | 32 (46.4%) | 1 | 0.893 | - | - | - |
Yes | 37 (53.6%) | 0.97 (0.6–1.56) | - | - | - | |
KIR2DS2 | ||||||
No | 33 (47.8%) | 1 | 0.178 | - | - | - |
Yes | 36 (52.2%) | 0.71 (0.44–1.17) | - | - | - | |
KIR2DS3 | ||||||
No | 39 (56.5%) | 1 | 0.136 | - | - | - |
Yes | 29 (42%) | 0.69 (0.43–1.12) | - | - | - | |
KIR2DS4 | ||||||
No | 6 (8.7%) | 1 | 0.806 | - | - | - |
Yes | 63 (91.3%) | 1.11 (0.48–2.59) | - | - | - | |
KIR2DS5 | ||||||
No | 46 (66.7%) | 1 | 0.512 | - | - | - |
Yes | 23 (33.3%) | 0.84 (0.51–1.4) | - | - | - | |
KIR3DL1 | ||||||
No | 7 (10.1%) | 1 | 0.947 | - | - | - |
Yes | 62 (89.9%) | 0.97 (0.44–2.14) | - | - | - | |
KIR3DS1 | ||||||
No | 42 (60.9%) | 1 | 0.969 | - | - | - |
Yes | 27 (39.1%) | 1.01 (0.62–1.64) | - | - | - | |
KIR2DP1 | ||||||
No | 7 (10.1%) | 1 | 0.977 | - | - | - |
Yes | 62 (89.9%) | 1.01 (0.46–2.22) | - | - | - | |
- | - | - | ||||
KIR3DS1–Bw4 | ||||||
No | 11 (40.7%) | 1 | 0.618 | - | - | - |
Yes | 16 (59.3%) | 0.82 (0.38–1.79) | - | - | - | |
3DS1–HLAB | ||||||
Heterozygous (w4w6) | 20 (28.9%) | 1 | 0.598 | - | - | - |
Homozygous (w4w4 or w6w6) | 7 (10.1%) | 1.28 (0.51–3.22) | - | - | - | |
Genotype | ||||||
AB | 27 (44.3%) | 1 | 27 (44.3%) | 1 | ||
AA | 16 (26.2%) | 2.27 (1.21–4.25) | 0.01 | 16 (26.2%) | 2.58 (1.31–5.10) | 0.006 |
BB | 18 (29.5%) | 1.99 (1.12–3.55) | 0.02 | 18 (29.5%) | 1.93 (1.04–3.58) | 0.03 |
Genotype | ||||||
AB | 27 (44.3%) | 1 | 0.004 | - | 1 | 0.005 |
AA or BB | 34 (55.7%) | 2.10 (1.28–3.47) | - | 2.16 (1.26–3.78) | ||
Semi-haplotype | ||||||
CENA/TELB or CENB/TELA | 26 (37.7%) | 1 | 0.03 | - | 1 | 0.04 |
CENA/TELA | 16 (26.2%) | 2.31 (1.08–4.95) | - | 2.50 (1.02–6.14) |
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Gómez-Aguilera, M.; Manzanares-Martín, B.; Cebrián-Aranda, A.; Rodríguez-Ariza, A.; González-Fernández, R.; del Puerto-Nevado, L.; García-Foncillas, J.; Arandaa, E. Immune Modulation Through KIR–HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer. Int. J. Mol. Sci. 2025, 26, 8062. https://doi.org/10.3390/ijms26168062
Gómez-Aguilera M, Manzanares-Martín B, Cebrián-Aranda A, Rodríguez-Ariza A, González-Fernández R, del Puerto-Nevado L, García-Foncillas J, Arandaa E. Immune Modulation Through KIR–HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer. International Journal of Molecular Sciences. 2025; 26(16):8062. https://doi.org/10.3390/ijms26168062
Chicago/Turabian StyleGómez-Aguilera, María, Bárbara Manzanares-Martín, Arancha Cebrián-Aranda, Antonio Rodríguez-Ariza, Rafael González-Fernández, Laura del Puerto-Nevado, Jesús García-Foncillas, and Enrique Arandaa. 2025. "Immune Modulation Through KIR–HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer" International Journal of Molecular Sciences 26, no. 16: 8062. https://doi.org/10.3390/ijms26168062
APA StyleGómez-Aguilera, M., Manzanares-Martín, B., Cebrián-Aranda, A., Rodríguez-Ariza, A., González-Fernández, R., del Puerto-Nevado, L., García-Foncillas, J., & Arandaa, E. (2025). Immune Modulation Through KIR–HLA Interactions Influences Cetuximab Efficacy in Colorectal Cancer. International Journal of Molecular Sciences, 26(16), 8062. https://doi.org/10.3390/ijms26168062