Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer

Aino Ojanperä; Päivi Sirniö; Hanna Elomaa; Ville K Äijälä; Henna Karjalainen; Vilja V Tapiainen; Meeri Kastinen; Akseli Kehusmaa; Oskari Rahkola; Vesa-Matti Pohjanen; Maarit Ahtiainen; Olli Helminen; Erkki-Ville Wirta; Jukka Rintala; Sanna Meriläinen; Raila Aro; Reetta Häivälä; Juha Saarnio; Tero Rautio; Toni T Seppälä; Jan Böhm; Jukka-Pekka Mecklin; Anne Tuomisto; Markus J Mäkinen; Juha P Väyrynen

doi:10.1158/1055-9965.EPI-25-0767

Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer

Aino Ojanperä
, Päivi Sirniö
, Hanna Elomaa
, Ville K Äijälä
, Henna Karjalainen
, Vilja V Tapiainen
, Meeri Kastinen
, Akseli Kehusmaa
, Oskari Rahkola
, Vesa-Matti Pohjanen
, Maarit Ahtiainen
, Olli Helminen
, Erkki-Ville Wirta
, Jukka Rintala
, Sanna Meriläinen
, Raila Aro
, Reetta Häivälä
, Juha Saarnio
, Tero Rautio
, Toni T Seppälä

Jan Böhm, Jukka-Pekka Mecklin, Anne Tuomisto, Markus J Mäkinen, Juha P Väyrynen

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

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Abstract

BACKGROUND: T-cell densities are associated with colorectal cancer outcome, but the significance of specific Th cell subsets is incompletely understood. We aimed to investigate the role of Th1 and Th2 cells and associated cytokine profiles.

METHODS: We used multiplex IHC to identify Th1 and Th2 cells on tumor samples of more than 2,000 patients with colorectal cancer (three independent cohorts). We measured serum levels of Th1 and Th2 cytokines in mesenteric (N = 77) and peripheral (N = 603) blood samples. We evaluated the prognostic significance of Th1 and Th2 cells and their associations with circulating cytokines.

RESULTS: High densities of both Th1 and Th2 cells were independently associated with better cancer-specific survival. In the largest cohort, the HR for high vs. low Th1 density was 0.62 (95% confidence interval, 0.44-0.85; PTrend = 0.004) and the HR for high vs. low Th2 density was 0.50 [95% confidence interval, 0.36-0.69; PTrend < 0.001]. Th1 cell density positively correlated with IL12 levels and negatively with IL10 levels in mesenteric serum. Th1:Th2 cell density ratio positively correlated with mesenteric serum Th1:Th2 produced cytokine ratio.

CONCLUSIONS: This study supports the prognostic significance of Th1 and Th2 cells in colorectal cancer. Mesenteric serum levels of Th-related cytokines may contribute to or reflect the tumor-associated Th1/Th2 response.

IMPACT: Findings highlight comparable roles for Th1 and Th2 cells in predicting favorable outcome and challenge the traditional notion of Th2 cells as tumor promoters.

Original language	English
Pages (from-to)	2032–2041
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	34
Issue number	11
DOIs	https://doi.org/10.1158/1055-9965.EPI-25-0767
Publication status	Published - 2025
Publication type	A1 Journal article-refereed

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Ojanperä, A., Sirniö, P., Elomaa, H., Äijälä, V. K., Karjalainen, H., Tapiainen, V. V., Kastinen, M., Kehusmaa, A., Rahkola, O., Pohjanen, V.-M., Ahtiainen, M., Helminen, O., Wirta, E.-V., Rintala, J., Meriläinen, S., Aro, R., Häivälä, R., Saarnio, J., Rautio, T., ... Väyrynen, J. P. (2025). Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer. Cancer Epidemiology, Biomarkers & Prevention, 34(11), 2032–2041. https://doi.org/10.1158/1055-9965.EPI-25-0767

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title = "Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer",

abstract = "BACKGROUND: T-cell densities are associated with colorectal cancer outcome, but the significance of specific Th cell subsets is incompletely understood. We aimed to investigate the role of Th1 and Th2 cells and associated cytokine profiles.METHODS: We used multiplex IHC to identify Th1 and Th2 cells on tumor samples of more than 2,000 patients with colorectal cancer (three independent cohorts). We measured serum levels of Th1 and Th2 cytokines in mesenteric (N = 77) and peripheral (N = 603) blood samples. We evaluated the prognostic significance of Th1 and Th2 cells and their associations with circulating cytokines.RESULTS: High densities of both Th1 and Th2 cells were independently associated with better cancer-specific survival. In the largest cohort, the HR for high vs. low Th1 density was 0.62 (95\% confidence interval, 0.44-0.85; PTrend = 0.004) and the HR for high vs. low Th2 density was 0.50 [95\% confidence interval, 0.36-0.69; PTrend < 0.001]. Th1 cell density positively correlated with IL12 levels and negatively with IL10 levels in mesenteric serum. Th1:Th2 cell density ratio positively correlated with mesenteric serum Th1:Th2 produced cytokine ratio.CONCLUSIONS: This study supports the prognostic significance of Th1 and Th2 cells in colorectal cancer. Mesenteric serum levels of Th-related cytokines may contribute to or reflect the tumor-associated Th1/Th2 response.IMPACT: Findings highlight comparable roles for Th1 and Th2 cells in predicting favorable outcome and challenge the traditional notion of Th2 cells as tumor promoters.",

author = "Aino Ojanper{\"a} and P{\"a}ivi Sirni{\"o} and Hanna Elomaa and {\"A}ij{\"a}l{\"a}, \{Ville K\} and Henna Karjalainen and Tapiainen, \{Vilja V\} and Meeri Kastinen and Akseli Kehusmaa and Oskari Rahkola and Vesa-Matti Pohjanen and Maarit Ahtiainen and Olli Helminen and Erkki-Ville Wirta and Jukka Rintala and Sanna Meril{\"a}inen and Raila Aro and Reetta H{\"a}iv{\"a}l{\"a} and Juha Saarnio and Tero Rautio and Sepp{\"a}l{\"a}, \{Toni T\} and Jan B{\"o}hm and Jukka-Pekka Mecklin and Anne Tuomisto and M{\"a}kinen, \{Markus J\} and V{\"a}yrynen, \{Juha P\}",

note = "{\textcopyright}2025 The Authors; Published by the American Association for Cancer Research.",

year = "2025",

doi = "10.1158/1055-9965.EPI-25-0767",

language = "English",

volume = "34",

pages = "2032–2041",

number = "11",

}

Ojanperä, A, Sirniö, P, Elomaa, H, Äijälä, VK, Karjalainen, H, Tapiainen, VV, Kastinen, M, Kehusmaa, A, Rahkola, O, Pohjanen, V-M, Ahtiainen, M, Helminen, O, Wirta, E-V, Rintala, J, Meriläinen, S, Aro, R, Häivälä, R, Saarnio, J, Rautio, T, Seppälä, TT, Böhm, J, Mecklin, J-P, Tuomisto, A, Mäkinen, MJ & Väyrynen, JP 2025, 'Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer', Cancer Epidemiology, Biomarkers & Prevention, vol. 34, no. 11, pp. 2032–2041. https://doi.org/10.1158/1055-9965.EPI-25-0767

TY - JOUR

T1 - Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer

AU - Ojanperä, Aino

AU - Sirniö, Päivi

AU - Elomaa, Hanna

AU - Äijälä, Ville K

AU - Karjalainen, Henna

AU - Tapiainen, Vilja V

AU - Kastinen, Meeri

AU - Kehusmaa, Akseli

AU - Rahkola, Oskari

AU - Pohjanen, Vesa-Matti

AU - Ahtiainen, Maarit

AU - Helminen, Olli

AU - Wirta, Erkki-Ville

AU - Rintala, Jukka

AU - Meriläinen, Sanna

AU - Aro, Raila

AU - Häivälä, Reetta

AU - Saarnio, Juha

AU - Rautio, Tero

AU - Seppälä, Toni T

AU - Böhm, Jan

AU - Mecklin, Jukka-Pekka

AU - Tuomisto, Anne

AU - Mäkinen, Markus J

AU - Väyrynen, Juha P

PY - 2025

Y1 - 2025

N2 - BACKGROUND: T-cell densities are associated with colorectal cancer outcome, but the significance of specific Th cell subsets is incompletely understood. We aimed to investigate the role of Th1 and Th2 cells and associated cytokine profiles.METHODS: We used multiplex IHC to identify Th1 and Th2 cells on tumor samples of more than 2,000 patients with colorectal cancer (three independent cohorts). We measured serum levels of Th1 and Th2 cytokines in mesenteric (N = 77) and peripheral (N = 603) blood samples. We evaluated the prognostic significance of Th1 and Th2 cells and their associations with circulating cytokines.RESULTS: High densities of both Th1 and Th2 cells were independently associated with better cancer-specific survival. In the largest cohort, the HR for high vs. low Th1 density was 0.62 (95% confidence interval, 0.44-0.85; PTrend = 0.004) and the HR for high vs. low Th2 density was 0.50 [95% confidence interval, 0.36-0.69; PTrend < 0.001]. Th1 cell density positively correlated with IL12 levels and negatively with IL10 levels in mesenteric serum. Th1:Th2 cell density ratio positively correlated with mesenteric serum Th1:Th2 produced cytokine ratio.CONCLUSIONS: This study supports the prognostic significance of Th1 and Th2 cells in colorectal cancer. Mesenteric serum levels of Th-related cytokines may contribute to or reflect the tumor-associated Th1/Th2 response.IMPACT: Findings highlight comparable roles for Th1 and Th2 cells in predicting favorable outcome and challenge the traditional notion of Th2 cells as tumor promoters.

AB - BACKGROUND: T-cell densities are associated with colorectal cancer outcome, but the significance of specific Th cell subsets is incompletely understood. We aimed to investigate the role of Th1 and Th2 cells and associated cytokine profiles.METHODS: We used multiplex IHC to identify Th1 and Th2 cells on tumor samples of more than 2,000 patients with colorectal cancer (three independent cohorts). We measured serum levels of Th1 and Th2 cytokines in mesenteric (N = 77) and peripheral (N = 603) blood samples. We evaluated the prognostic significance of Th1 and Th2 cells and their associations with circulating cytokines.RESULTS: High densities of both Th1 and Th2 cells were independently associated with better cancer-specific survival. In the largest cohort, the HR for high vs. low Th1 density was 0.62 (95% confidence interval, 0.44-0.85; PTrend = 0.004) and the HR for high vs. low Th2 density was 0.50 [95% confidence interval, 0.36-0.69; PTrend < 0.001]. Th1 cell density positively correlated with IL12 levels and negatively with IL10 levels in mesenteric serum. Th1:Th2 cell density ratio positively correlated with mesenteric serum Th1:Th2 produced cytokine ratio.CONCLUSIONS: This study supports the prognostic significance of Th1 and Th2 cells in colorectal cancer. Mesenteric serum levels of Th-related cytokines may contribute to or reflect the tumor-associated Th1/Th2 response.IMPACT: Findings highlight comparable roles for Th1 and Th2 cells in predicting favorable outcome and challenge the traditional notion of Th2 cells as tumor promoters.

U2 - 10.1158/1055-9965.EPI-25-0767

DO - 10.1158/1055-9965.EPI-25-0767

M3 - Article

C2 - 40928327

SN - 1055-9965

VL - 34

SP - 2032

EP - 2041

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 11

ER -

Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer

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