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Purpose <p><i>Blastocystis</i> sp. is an opportunistic intestinal protist frequently associated with colorectal cancer (CRC). Its immunomodulatory influence within the immunosuppressive milieu of chemotherapy-treated CRC remains largely unexplored. This study investigated the effects of <i>Blastocystis</i> solubilized antigen (BSA) from subtypes ST1–ST5 on the metabolic activity and cytokine gene expression of peripheral blood mononuclear cells (PBMCs).</p> Methods <p>PBMCs were isolated from healthy donors (HDs; <i>n</i>=5) and CRC patients undergoing 5-fluorouracil-based chemotherapy (CRCPs; <i>n</i>=5) sampled 7–14 days post-cycle to capture the treatment nadir. PBMCs were challenged with BSA (0.001–30 µg/ml) for 48 hours. Metabolic activity was assessed via MTT assay, and transcriptional profiles of cytokines (IL-6, IL-8, TGF-β, IFN-γ, TNF-α) were evaluated using real-time RT-PCR.</p> Results <p>HD PBMCs exhibited a biphasic metabolic response, shifting to significant stimulation at BSA concentrations exceeding 10 µg/ml. Conversely, CRCP PBMCs displayed a significantly attenuated, predominantly inhibitory metabolic profile across all concentrations (<i>p</i> &lt; 0.001), despite maintaining viability to PHA. Transcriptionally, HDs showed balanced upregulation of effector and pro-tumorigenic transcripts. In contrast, the CRCP cohort exhibited widespread transcriptional blunting. Notably, subtype ST3 was a distinct outlier in CRCPs, uniquely inducing robust IFN-γ and TNF-α expression (<i>p</i> &lt; 0.01) comparable to HDs.</p> Conclusion <p>While chemotherapy induces systemic hyporesponsiveness, ST3 possesses unique immunogenic properties that bypass immune suppression. This transcriptional escape may facilitate an unbalanced inflammatory milieu conducive to CRC progression.</p>

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Differential Metabolic and Transcriptional Responses of PBMCs to Blastocystis sp. Subtypes in Chemotherapy-Treated Colorectal Cancer Patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Muhammad Mirza Halimi,
  • Deviga Genasan,
  • Arutchelvan Rajamanikam,
  • Deepa Anbazhagan,
  • Vetriselvan Subramaniyan,
  • Suresh Kumar Govind,
  • Umah Rani Kuppusamy,
  • Rohit Gundamaraju,
  • Vinoth Kumarasamy

摘要

Purpose

Blastocystis sp. is an opportunistic intestinal protist frequently associated with colorectal cancer (CRC). Its immunomodulatory influence within the immunosuppressive milieu of chemotherapy-treated CRC remains largely unexplored. This study investigated the effects of Blastocystis solubilized antigen (BSA) from subtypes ST1–ST5 on the metabolic activity and cytokine gene expression of peripheral blood mononuclear cells (PBMCs).

Methods

PBMCs were isolated from healthy donors (HDs; n=5) and CRC patients undergoing 5-fluorouracil-based chemotherapy (CRCPs; n=5) sampled 7–14 days post-cycle to capture the treatment nadir. PBMCs were challenged with BSA (0.001–30 µg/ml) for 48 hours. Metabolic activity was assessed via MTT assay, and transcriptional profiles of cytokines (IL-6, IL-8, TGF-β, IFN-γ, TNF-α) were evaluated using real-time RT-PCR.

Results

HD PBMCs exhibited a biphasic metabolic response, shifting to significant stimulation at BSA concentrations exceeding 10 µg/ml. Conversely, CRCP PBMCs displayed a significantly attenuated, predominantly inhibitory metabolic profile across all concentrations (p < 0.001), despite maintaining viability to PHA. Transcriptionally, HDs showed balanced upregulation of effector and pro-tumorigenic transcripts. In contrast, the CRCP cohort exhibited widespread transcriptional blunting. Notably, subtype ST3 was a distinct outlier in CRCPs, uniquely inducing robust IFN-γ and TNF-α expression (p < 0.01) comparable to HDs.

Conclusion

While chemotherapy induces systemic hyporesponsiveness, ST3 possesses unique immunogenic properties that bypass immune suppression. This transcriptional escape may facilitate an unbalanced inflammatory milieu conducive to CRC progression.