Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4

Frédéric Illouz; Daniel Y Wang; Fei Ye; Shilin Zhao; Douglas B Johnson; A. Gupta; K. M. De Felice; E. V. Loftus; S. Khanna; Kimberly E. Beck; Joseph A. Blansfield; Khoi Q. Tran; Andrew L. Feldman; Marybeth S. Hughes; Richard E. Royal; Udai S. Kammula; Suzanne L. Topalian; Richard M. Sherry; David Kleiner; Martha Quezado; Israel Lowy; Michael Yellin; Steven A. Rosenberg; James C. Yang; J. M. Michot; C. Bigenwald; S. Champiat; M. Collins; Franck Carbonnel; S. Postel-Vinay; A. Berdelou; A. Varga; R. Bahleda; A. Hollebecque; C. Massard; A. Fuerea; V. Ribrag; A. Gazzah; J. P. Armand; N. Amellal; E. Angevin; N. Noel; C. Boutros; C. Mateus; C. Robert; J. C. Soria; A. Marabelle; O. Lambotte; Raul S. Gonzalez; Safia N. Salaria; Caitlin D. Bohannon; Aaron R. Huber; Michael M. Feely; Chanjuan Shi; L. Marthey; C. Mateus; C. Mussini; M. Nachury; S. Nancey; F. Grange; C. Zallot; L. Peyrin-Biroulet; J. F. Rahier; M. Bourdier de Beauregard; L. Mortier; C. Coutzac; E. Soularue; E. Lanoy; N. Kapel; D. Planchard; N. Chaput; C. Robert; Franck Carbonnel; Al B. Benson; Jaffer A. Ajani; Robert B. Catalano; Constance Engelking; Steven M. Kornblau; James A. Martenson; Richard McCallum; Edith P. Mitchell; Thomas M. O'Dorisio; Everett E. Vokes; Scott Wadler; J B A G Haanen; Franck Carbonnel; C. Robert; K M Kerr; S Peters; J Larkin; K Jordan; Viktoria Bergqvist; Erik Hertervig; Peter Gedeon; Marija Kopljar; Håkan Griph; Sara Kinhult; Ana Carneiro; Jan Marsal; Amy Hsin Chieh Hsieh; Mutaz Ferman; Michael P. Brown; Jane M. Andrews; Harris Trainer; Paul Hulse; Claire E Higham; Peter Trainer; Paul Lorigan; Jing Hughes; Nalini Vudattu; Mario Sznol; Scott Gettinger; Harriet Kluger; Beatrice Lupsa; Kevan C Herold

doi:10.1200/JCO.2005.04.5716

Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4

Frédéric Illouz, Daniel Y Wang, Fei Ye, Shilin Zhao, Douglas B Johnson, A. Gupta, K. M. De Felice, E. V. Loftus, S. Khanna, Kimberly E. Beck, Joseph A. Blansfield, Khoi Q. Tran, Andrew L. Feldman, Marybeth S. Hughes, Richard E. Royal, Udai S. Kammula, Suzanne L. Topalian, Richard M. Sherry, David Kleiner, Martha QuezadoIsrael Lowy, Michael Yellin, Steven A. Rosenberg, James C. Yang, J. M. Michot, C. Bigenwald, S. Champiat, M. Collins, Franck Carbonnel, S. Postel-Vinay, A. Berdelou, A. Varga, R. Bahleda, A. Hollebecque, C. Massard, A. Fuerea, V. Ribrag, A. Gazzah, J. P. Armand, N. Amellal, E. Angevin, N. Noel, C. Boutros, C. Mateus, C. Robert, J. C. Soria, A. Marabelle, O. Lambotte, Raul S. Gonzalez, Safia N. Salaria, Caitlin D. Bohannon, Aaron R. Huber, Michael M. Feely, Chanjuan Shi, L. Marthey, C. Mateus, C. Mussini, M. Nachury, S. Nancey, F. Grange, C. Zallot, L. Peyrin-Biroulet, J. F. Rahier, M. Bourdier de Beauregard, L. Mortier, C. Coutzac, E. Soularue, E. Lanoy, N. Kapel, D. Planchard, N. Chaput, C. Robert, Franck Carbonnel, Al B. Benson, Jaffer A. Ajani, Robert B. Catalano, Constance Engelking, Steven M. Kornblau, James A. Martenson, Richard McCallum, Edith P. Mitchell, Thomas M. O'Dorisio, Everett E. Vokes, Scott Wadler, J B A G Haanen, Franck Carbonnel, C. Robert, K M Kerr, S Peters, J Larkin, K Jordan, Viktoria Bergqvist, Erik Hertervig, Peter Gedeon, Marija Kopljar, Håkan Griph, Sara Kinhult, Ana Carneiro, Jan Marsal, Amy Hsin Chieh Hsieh, Mutaz Ferman, Michael P. Brown, Jane M. Andrews, Harris Trainer, Paul Hulse, Claire E Higham, Peter Trainer, Paul Lorigan, Jing Hughes, Nalini Vudattu, Mario Sznol, Scott Gettinger, Harriet Kluger, Beatrice Lupsa, Kevan C Herold

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. PATIENTS AND METHODS: We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. RESULTS: The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). CONCLUSION: CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.

Original language	English
Pages (from-to)	2283-2289
Number of pages	7
Journal	Journal of Clinical Oncology
DOIs	https://doi.org/10.1200/JCO.2005.04.5716
Publication status	Published - 20 May 2006

Keywords

80 and over
Adult
Aged
Anti-CTLA-4
Anti-PD-1 antibody
Antibodies
Antigens
Autoimmune
Autoimmune Diseases
Autoimmunity
CD
CTLA-4 Antigen
Colitis
Cytotoxic
Cytotoxic T-lymphocyte-associated antigen 4
Dermatitis
Diabetes Mellitus
Differentiation
Disease Progression
Enterocolitis
Female
HLA-A2 Antigen
Hepatitis
Humans
Immune Tolerance
Immune checkpoint blockade
Immune-checkpoint inhibitor induced enterocolitis
Immune-related adverse events
Immunotherapy
Injections
Intravenous
Ipilimumab
Lung cancer
Lymphocyte Activation
Male
Melanoma
Membrane Glycoproteins
Middle Aged
Monoclonal
Neoplasm
Neoplasm Metastasis
Neoplasm Proteins
Neoplasms
Nivolumab
Peptide Fragments
Peptides
Programmed Cell Death 1 Receptor
Salvage Therapy
Subcutaneous
T-Lymphocyte Subsets
T-Lymphocytes
Tumour neoantigen
Type 1
Vaccination
Vedolizumab treatment against irAEs
Vitiligo
administration & dosage
adverse effects
blood
chemically induced
chemistry
colitis
etiology
gastroenteritis
gastrointestinal tract
gp100 Melanoma Antigen
immunology
immunotherapy
pathology
physiology
programmed cell death protein 1
therapeutic use
therapy

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1200/JCO.2005.04.5716

Cite this

Illouz, F., Wang, D. Y., Ye, F., Zhao, S., Johnson, D. B., Gupta, A., De Felice, K. M., Loftus, E. V., Khanna, S., Beck, K. E., Blansfield, J. A., Tran, K. Q., Feldman, A. L., Hughes, M. S., Royal, R. E., Kammula, U. S., Topalian, S. L., Sherry, R. M., Kleiner, D., ... Herold, K. C. (2006). Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. Journal of Clinical Oncology, 2283-2289. https://doi.org/10.1200/JCO.2005.04.5716

@article{c96492baf50241539d45ee97a4c60cce,

title = "Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4",

abstract = "PURPOSE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. PATIENTS AND METHODS: We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. RESULTS: The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). CONCLUSION: CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.",

keywords = "80 and over, Adult, Aged, Anti-CTLA-4, Anti-PD-1 antibody, Antibodies, Antigens, Autoimmune, Autoimmune Diseases, Autoimmunity, CD, CTLA-4 Antigen, Colitis, Cytotoxic, Cytotoxic T-lymphocyte-associated antigen 4, Dermatitis, Diabetes Mellitus, Differentiation, Disease Progression, Enterocolitis, Female, HLA-A2 Antigen, Hepatitis, Humans, Immune Tolerance, Immune checkpoint blockade, Immune-checkpoint inhibitor induced enterocolitis, Immune-related adverse events, Immunotherapy, Injections, Intravenous, Ipilimumab, Lung cancer, Lymphocyte Activation, Male, Melanoma, Membrane Glycoproteins, Middle Aged, Monoclonal, Neoplasm, Neoplasm Metastasis, Neoplasm Proteins, Neoplasms, Nivolumab, Peptide Fragments, Peptides, Programmed Cell Death 1 Receptor, Salvage Therapy, Subcutaneous, T-Lymphocyte Subsets, T-Lymphocytes, Tumour neoantigen, Type 1, Vaccination, Vedolizumab treatment against irAEs, Vitiligo, administration & dosage, adverse effects, blood, chemically induced, chemistry, colitis, etiology, gastroenteritis, gastrointestinal tract, gp100 Melanoma Antigen, immunology, immunotherapy, pathology, physiology, programmed cell death protein 1, therapeutic use, therapy",

author = "Fr{\'e}d{\'e}ric Illouz and Wang, {Daniel Y} and Fei Ye and Shilin Zhao and Johnson, {Douglas B} and A. Gupta and {De Felice}, {K. M.} and Loftus, {E. V.} and S. Khanna and Beck, {Kimberly E.} and Blansfield, {Joseph A.} and Tran, {Khoi Q.} and Feldman, {Andrew L.} and Hughes, {Marybeth S.} and Royal, {Richard E.} and Kammula, {Udai S.} and Topalian, {Suzanne L.} and Sherry, {Richard M.} and David Kleiner and Martha Quezado and Israel Lowy and Michael Yellin and Rosenberg, {Steven A.} and Yang, {James C.} and Michot, {J. M.} and C. Bigenwald and S. Champiat and M. Collins and Franck Carbonnel and S. Postel-Vinay and A. Berdelou and A. Varga and R. Bahleda and A. Hollebecque and C. Massard and A. Fuerea and V. Ribrag and A. Gazzah and Armand, {J. P.} and N. Amellal and E. Angevin and N. Noel and C. Boutros and C. Mateus and C. Robert and Soria, {J. C.} and A. Marabelle and O. Lambotte and Gonzalez, {Raul S.} and Salaria, {Safia N.} and Bohannon, {Caitlin D.} and Huber, {Aaron R.} and Feely, {Michael M.} and Chanjuan Shi and L. Marthey and C. Mateus and C. Mussini and M. Nachury and S. Nancey and F. Grange and C. Zallot and L. Peyrin-Biroulet and Rahier, {J. F.} and {de Beauregard}, {M. Bourdier} and L. Mortier and C. Coutzac and E. Soularue and E. Lanoy and N. Kapel and D. Planchard and N. Chaput and C. Robert and Franck Carbonnel and Benson, {Al B.} and Ajani, {Jaffer A.} and Catalano, {Robert B.} and Constance Engelking and Kornblau, {Steven M.} and Martenson, {James A.} and Richard McCallum and Mitchell, {Edith P.} and O'Dorisio, {Thomas M.} and Vokes, {Everett E.} and Scott Wadler and Haanen, {J B A G} and Franck Carbonnel and C. Robert and Kerr, {K M} and S Peters and J Larkin and K Jordan and Viktoria Bergqvist and Erik Hertervig and Peter Gedeon and Marija Kopljar and H{\aa}kan Griph and Sara Kinhult and Ana Carneiro and Jan Marsal and Hsieh, {Amy Hsin Chieh} and Mutaz Ferman and Brown, {Michael P.} and Andrews, {Jane M.} and Harris Trainer and Paul Hulse and Higham, {Claire E} and Peter Trainer and Paul Lorigan and Jing Hughes and Nalini Vudattu and Mario Sznol and Scott Gettinger and Harriet Kluger and Beatrice Lupsa and Herold, {Kevan C}",

year = "2006",

month = may,

day = "20",

doi = "10.1200/JCO.2005.04.5716",

language = "English",

pages = "2283--2289",

journal = "Journal of Clinical Oncology",

issn = "1527-7755",

publisher = "American Society of Clinical Oncology",

}

Illouz, F, Wang, DY, Ye, F, Zhao, S, Johnson, DB, Gupta, A, De Felice, KM, Loftus, EV, Khanna, S, Beck, KE, Blansfield, JA, Tran, KQ, Feldman, AL, Hughes, MS, Royal, RE, Kammula, US, Topalian, SL, Sherry, RM, Kleiner, D, Quezado, M, Lowy, I, Yellin, M, Rosenberg, SA, Yang, JC, Michot, JM, Bigenwald, C, Champiat, S, Collins, M, Carbonnel, F, Postel-Vinay, S, Berdelou, A, Varga, A, Bahleda, R, Hollebecque, A, Massard, C, Fuerea, A, Ribrag, V, Gazzah, A, Armand, JP, Amellal, N, Angevin, E, Noel, N, Boutros, C, Mateus, C, Robert, C, Soria, JC, Marabelle, A, Lambotte, O, Gonzalez, RS, Salaria, SN, Bohannon, CD, Huber, AR, Feely, MM, Shi, C, Marthey, L, Mateus, C, Mussini, C, Nachury, M, Nancey, S, Grange, F, Zallot, C, Peyrin-Biroulet, L, Rahier, JF, de Beauregard, MB, Mortier, L, Coutzac, C, Soularue, E, Lanoy, E, Kapel, N, Planchard, D, Chaput, N, Robert, C, Carbonnel, F, Benson, AB, Ajani, JA, Catalano, RB, Engelking, C, Kornblau, SM, Martenson, JA, McCallum, R, Mitchell, EP, O'Dorisio, TM, Vokes, EE, Wadler, S, Haanen, JBAG, Carbonnel, F, Robert, C, Kerr, KM, Peters, S, Larkin, J, Jordan, K, Bergqvist, V, Hertervig, E, Gedeon, P, Kopljar, M, Griph, H, Kinhult, S, Carneiro, A, Marsal, J, Hsieh, AHC, Ferman, M, Brown, MP, Andrews, JM, Trainer, H, Hulse, P, Higham, CE, Trainer, P, Lorigan, P, Hughes, J, Vudattu, N, Sznol, M, Gettinger, S, Kluger, H, Lupsa, B & Herold, KC 2006, 'Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4', Journal of Clinical Oncology, pp. 2283-2289. https://doi.org/10.1200/JCO.2005.04.5716

TY - JOUR

T1 - Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4

AU - Illouz, Frédéric

AU - Wang, Daniel Y

AU - Ye, Fei

AU - Zhao, Shilin

AU - Johnson, Douglas B

AU - Gupta, A.

AU - De Felice, K. M.

AU - Loftus, E. V.

AU - Khanna, S.

AU - Beck, Kimberly E.

AU - Blansfield, Joseph A.

AU - Tran, Khoi Q.

AU - Feldman, Andrew L.

AU - Hughes, Marybeth S.

AU - Royal, Richard E.

AU - Kammula, Udai S.

AU - Topalian, Suzanne L.

AU - Sherry, Richard M.

AU - Kleiner, David

AU - Quezado, Martha

AU - Lowy, Israel

AU - Yellin, Michael

AU - Rosenberg, Steven A.

AU - Yang, James C.

AU - Michot, J. M.

AU - Bigenwald, C.

AU - Champiat, S.

AU - Collins, M.

AU - Carbonnel, Franck

AU - Postel-Vinay, S.

AU - Berdelou, A.

AU - Varga, A.

AU - Bahleda, R.

AU - Hollebecque, A.

AU - Massard, C.

AU - Fuerea, A.

AU - Ribrag, V.

AU - Gazzah, A.

AU - Armand, J. P.

AU - Amellal, N.

AU - Angevin, E.

AU - Noel, N.

AU - Boutros, C.

AU - Mateus, C.

AU - Robert, C.

AU - Soria, J. C.

AU - Marabelle, A.

AU - Lambotte, O.

AU - Gonzalez, Raul S.

AU - Salaria, Safia N.

AU - Bohannon, Caitlin D.

AU - Huber, Aaron R.

AU - Feely, Michael M.

AU - Shi, Chanjuan

AU - Marthey, L.

AU - Mateus, C.

AU - Mussini, C.

AU - Nachury, M.

AU - Nancey, S.

AU - Grange, F.

AU - Zallot, C.

AU - Peyrin-Biroulet, L.

AU - Rahier, J. F.

AU - de Beauregard, M. Bourdier

AU - Mortier, L.

AU - Coutzac, C.

AU - Soularue, E.

AU - Lanoy, E.

AU - Kapel, N.

AU - Planchard, D.

AU - Chaput, N.

AU - Robert, C.

AU - Carbonnel, Franck

AU - Benson, Al B.

AU - Ajani, Jaffer A.

AU - Catalano, Robert B.

AU - Engelking, Constance

AU - Kornblau, Steven M.

AU - Martenson, James A.

AU - McCallum, Richard

AU - Mitchell, Edith P.

AU - O'Dorisio, Thomas M.

AU - Vokes, Everett E.

AU - Wadler, Scott

AU - Haanen, J B A G

AU - Carbonnel, Franck

AU - Robert, C.

AU - Kerr, K M

AU - Peters, S

AU - Larkin, J

AU - Jordan, K

AU - Bergqvist, Viktoria

AU - Hertervig, Erik

AU - Gedeon, Peter

AU - Kopljar, Marija

AU - Griph, Håkan

AU - Kinhult, Sara

AU - Carneiro, Ana

AU - Marsal, Jan

AU - Hsieh, Amy Hsin Chieh

AU - Ferman, Mutaz

AU - Brown, Michael P.

AU - Andrews, Jane M.

AU - Trainer, Harris

AU - Hulse, Paul

AU - Higham, Claire E

AU - Trainer, Peter

AU - Lorigan, Paul

AU - Hughes, Jing

AU - Vudattu, Nalini

AU - Sznol, Mario

AU - Gettinger, Scott

AU - Kluger, Harriet

AU - Lupsa, Beatrice

AU - Herold, Kevan C

PY - 2006/5/20

Y1 - 2006/5/20

N2 - PURPOSE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. PATIENTS AND METHODS: We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. RESULTS: The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). CONCLUSION: CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.

AB - PURPOSE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. PATIENTS AND METHODS: We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. RESULTS: The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). CONCLUSION: CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.

KW - 80 and over

KW - Adult

KW - Aged

KW - Anti-CTLA-4

KW - Anti-PD-1 antibody

KW - Antibodies

KW - Antigens

KW - Autoimmune

KW - Autoimmune Diseases

KW - Autoimmunity

KW - CD

KW - CTLA-4 Antigen

KW - Colitis

KW - Cytotoxic

KW - Cytotoxic T-lymphocyte-associated antigen 4

KW - Dermatitis

KW - Diabetes Mellitus

KW - Differentiation

KW - Disease Progression

KW - Enterocolitis

KW - Female

KW - HLA-A2 Antigen

KW - Hepatitis

KW - Humans

KW - Immune Tolerance

KW - Immune checkpoint blockade

KW - Immune-checkpoint inhibitor induced enterocolitis

KW - Immune-related adverse events

KW - Immunotherapy

KW - Injections

KW - Intravenous

KW - Ipilimumab

KW - Lung cancer

KW - Lymphocyte Activation

KW - Male

KW - Melanoma

KW - Membrane Glycoproteins

KW - Middle Aged

KW - Monoclonal

KW - Neoplasm

KW - Neoplasm Metastasis

KW - Neoplasm Proteins

KW - Neoplasms

KW - Nivolumab

KW - Peptide Fragments

KW - Peptides

KW - Programmed Cell Death 1 Receptor

KW - Salvage Therapy

KW - Subcutaneous

KW - T-Lymphocyte Subsets

KW - T-Lymphocytes

KW - Tumour neoantigen

KW - Type 1

KW - Vaccination

KW - Vedolizumab treatment against irAEs

KW - Vitiligo

KW - administration & dosage

KW - adverse effects

KW - blood

KW - chemically induced

KW - chemistry

KW - colitis

KW - etiology

KW - gastroenteritis

KW - gastrointestinal tract

KW - gp100 Melanoma Antigen

KW - immunology

KW - immunotherapy

KW - pathology

KW - physiology

KW - programmed cell death protein 1

KW - therapeutic use

KW - therapy

UR - https://www.keytruda.com/static/pdf/adverse-reaction-management-tool.pdf + http://dx.doi.org/10.1093/annonc/mdx225 https://doi.org/10.1080/2162402X.2017.1344805

UR - http://www.mendeley.com/research/enterocolitis-patients-cancer-after-antibody-blockade-cytotoxic-tlymphocyteassociated-antigen-4-2

U2 - 10.1200/JCO.2005.04.5716

DO - 10.1200/JCO.2005.04.5716

M3 - Article

C2 - 16710025

SN - 1527-7755

SP - 2283

EP - 2289

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

ER -

Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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