SIGNATURES FOR PREDICTING CANCER IMMUNE THERAPY RESPONSE

1 - 21 . (canceled)

22 . A system for detecting resistance, or an increased likelihood of resistance, to a treatment regimen comprising an immune checkpoint inhibitor, the system comprising:

(1) a sample analyzer for assaying one or more patient samples comprising or derived from a cancer cell to determine or detect the sequence of at least a portion of each test gene in a panel of genes comprising the following antigen processing machinery genes: Beta-2-Microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA), Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), Endoplasmic Reticulum Aminopeptidase 2 (ERAP2), NLR family CARD domain containing 5 (NLRC5), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP1), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP2), and TAP binding protein (TAPBP);

(2) a first computer program for receiving test genetic sequence data on the test genes;

(3) a second computer program for comparing the test genetic sequence data to one or more reference genetic sequences for each test gene to determine whether any of the test genes harbors a mutation; and

(4) a third computer program for determining:

(a) that a patient in whose sample at least one test gene is determined by the second computer program in (3) to harbor a mutation has an increased likelihood of resistance to a treatment regimen comprising an immune checkpoint inhibitor; or

(b) that a patient in whose sample no test gene is determined by the second computer program in (3) to harbor a mutation has a decreased likelihood of resistance to a treatment regimen comprising an immune checkpoint inhibitor,

wherein the system further comprises a display module displaying the comparison between the test genetic sequence date and the reference sequence(s), or displaying a result of the computerized comparison.

23 . The system of claim 22 , wherein the third computer program determine whether the sample has a mutation selected from:

Gene

Exon

Variant

HGVS

B2M

1

Base 43 del2

c.43_44del (p.Leu15Phefs*41)

B2M

2

Base 209 del1

c.276del (p.Thr93Leufs*10)

B2M

2

Base −2 A > G

c.68 − 2A > G

CIITA

11

Base 956 insC

c. 1962dupC (p.Gly655Argfs*94), c.1965dupC

(p.Gly656Argfs*94)

ERAP1

12

Base 102 del4

c. 1861_1864del (p.Thr621Alafs*3)

ERAP2

3

Base 91 del1

c.805del (p.Cys269Valfs*6)

ERAP2

8

Base 66

c.1437_1438delinsAT (p.Ile480*)

del2insAT

NLRC5

4

Base

c. 1067_1070del (p.Pro356Glnfs*20)

643 del4

NLRC5

4

Base 782 del1

c. 1206del (p.Cys403 Valfs*33)

NLRC5

4

Base 1221 C > T

c. 1645C > T (p.Gln549*)

NLRC5

4

Base 1350 C > T

c. 1774C > T (p.Gln592*)

NLRC5

11

Base 23 del1

c.2566del (p. Val856Serfs*8)

NLRC5

23

Base 78 del1

c.3584del (p.Lys1195Argfs*38)

NLRC5

36

Base 23 G > T

c.4606G > T (p.Glu1536*)

NLRC5

42

Base 68 del1

c.5149del (p.His1717Ilefs*29)

TAPBP

4

Base 92 del1

c.561del (p.Thr188Profs*17), c.300del

(p. Thr101Profs*17)

B2M

1

Base 3 G > C

c.3G > C (p.Met1?)

B2M

1

Base 69 T > C

c.67 + 2T > C

B2M

2

Base 148 del12

c.215_226del (p.Ser72_Ser75del)

B2M

2

Base 235 G > T

c.302G > T (p.Arg101Leu)

B2M

2

Base 250 del34

c.317 346 + 4del

CIITA

11

Base 132 C > T

c.1138C > T (p.Arg380Trp), c.1141C > T

(p.Arg381Trp)

CIITA

11

Base

c. 1328C > G (p.Pro443 Arg), c. 1331C > G

322 C > G

(p.Pro444Arg)

ERAP2

6

Base 107 T > G

c. 1232T > G (p.Leu411Arg)

ERAP2

14

Base 82 C > T

c.2251C > T (p.Arg751Cys)

NLRC5

17

Base 69

c.3098C > A (p.Ala1033Asp)

C > A

NLRC5

22

Base 56 C > T

c.3478C > T (p.Pro1160Ser)

NLRC5

36

Base 30 G > A

c.4613G > A (p.Gly1538Asp)

NLRC5

47

Base −1 G > A

c.5490 − 1G > A

TAP1

7

Base 170 C > T

c. 1727C > T (p.Pro576Leu), c.944C > T

(p.Pro315Leu)

TAP1

7

Base 188 A > C

c. 1745A > C (p.Gln582Pro), c.962A > C

(p.Gln321Pro)

TAP1

10

Base 40 G > A

c.2123G > A (p.Arg708Gln), c. 1340G > A

(p.Arg447Gln)

TAP2

3

Base −1 G > A

c.609 − 1G > A

TAP2

4

Base 199 G > A

c.938G > A (p.Arg313His)

TAP2

7

Base 127 del1

c. 1399del (p. Val467Leufs*2)

TAPBP

2

Base 66 G > A

c. 103G > A (p.Gly35Arg)

TAPBP

2

Base 124 C > G

c. 161C > G (p.Pro54Arg)

TAPBP

2

Base 137

c.174_175delinsTT (p.Asp59delinsTyr)

del2insTT

TAPBP

4

Base 261

c.730 731delinsAT (p.Asp244delinsIle),

del2insAT

c.469 470delinsAT (p.Asp157delinsIle)

.

24 . The system of claim 22 , wherein the sample analyzer comprises the sample or DNA, RNA or protein molecules extracted or derived from the sample.

25 . The system of claim 22 , wherein the cancer is melanoma, renal cancer, lung cancer, bladder cancer, breast cancer, gastric cancer, prostate cancer, head and neck squamous cell carcinoma (HNSCC), or hematologic cancer.

26 . The system of claim 22 , wherein the sequences of the test genes are detected by Sanger sequencing, sequencing by synthesis, or single-molecule sequencing.

27 . The system of claim 22 , wherein the panel of genes further comprises at least one additional gene selected from: Major Histocompatibility Complex, Class I, A (HLA-A), Major Histocompatibility Complex, Class I, B (HLA-B), Major Histocompatibility Complex, Class I, C (HLA-C), Major Histocompatibility Complex, Class I, E (HLA-E), Major Histocompatibility Complex, Class I, G (HLA-G), or Protein Disulfide Isomerase Family A Member 3 (PDIA3).

28 . The system of claim 22 , wherein the immune checkpoint inhibitor is selected from Table 2.

29 . A method for treating a cancer patient, comprising:

a) sequencing genomic DNA isolated from a sample comprising cancer cell from a subject that is a candidate for a treatment regimen comprising an immune checkpoint inhibitor for a sequence of at least a portion of each test gene in a panel of genes comprising the following antigen processing machinery genes: Beta-2-Microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA), Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), Endoplasmic Reticulum Aminopeptidase 2 (ERAP2), NLR family CARD domain containing 5 (NLRC5), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP1), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP2), and TAP binding protein (TAPBP);

b) detecting a mutation in any of the test genes that results in low expression of the test gene or any protein encoded thereby, and

c) administering a treatment regimen comprising an immune checkpoint inhibitor to the patient in whose sample no test gene is determined in (b) to have low expression.

30 . The method of claim 29 , wherein the immune checkpoint inhibitor is selected from Table 2.

31 . The method of claim 29 , wherein the cancer is melanoma, renal cancer, lung cancer, bladder cancer, breast cancer, gastric cancer, prostate cancer, head and neck squamous cell carcinoma (HNSCC), or hematologic cancer.

32 . The method of claim 29 , wherein the sequences of the test genes are detected by Sanger sequencing, sequencing by synthesis, or single-molecule sequencing.

33 . The method of claim 29 , wherein the panel of genes further comprises at least one additional gene selected from: Major Histocompatibility Complex, Class I, A (HLA-A), Major Histocompatibility Complex, Class I, B (HLA-B), Major Histocompatibility Complex, Class I, C (HLA-C), Major Histocompatibility Complex, Class I, E (HLA-E), Major Histocompatibility Complex, Class I, G (HLA-G), or Protein Disulfide Isomerase Family A Member 3 (PDIA3).