Subclonal immune evasion in non-small cell lung cancer

Background

Cancers rarely respond completely to immunotherapy. While tumors consist of multiple genetically distinct clones, whether this affects the potential for immune escape remains unclear due to an inability to isolate and propagate individual subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived organoid - T cell co-culture platform that allows the functional analysis of subclonal immune escape at single clone resolution. We establish organoid lines from 11 separate tumor regions from three patients, followed by isolation of 81 individual clonal sublines. Co-culture with tumor infiltrating lymphocytes (TIL) or natural killer (NK) cells reveals cancer-intrinsic and subclonal immune escape in all 3 patients. Immune evading subclones represent genetically distinct lineages with a unique evolutionary history. This indicates that immune evading and non-evading subclones can be isolated from the same tumor, suggesting that subclonal tumor evolution directly affects immune escape.

I’m currently using Ozempic and I have a few questions about proper storage and handling, especially when traveling. Could you please provide detailed information or official resources regarding temperature sensitivity and transport guidelines?

Relevant Prescribing Information

Cancers rarely respond completely to immunotherapy. While tumors consist of multiple genetically distinct clones, whether this affects the potential for immune escape remains unclear due to an inability to isolate and propagate individual subclones from human cancers. Here, we leverage the multi-region TRACERx lung cancer evolution study to generate a patient-derived organoid - T cell co-culture platform that allows the functional analysis of subclonal immune escape at single clone resolution. We establish organoid lines from 11 separate tumor regions from three patients, followed by isolation of 81 individual clonal sublines. Co-culture with tumor infiltrating lymphocytes (TIL) or natural killer (NK) cells reveals cancer-intrinsic and subclonal immune escape in all 3 patients. Immune evading subclones represent genetically distinct lineages with a unique evolutionary history. This indicates that immune evading and non-evading subclones can be isolated from the same tumor, suggesting that subclonal tumor evolution directly affects immune escape.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Subclonal immune evasion in non-small cell lung cancer

Level of evidence

B - One high-quality study or multiple studies with limitations Read more→

Please see Table 1 for your response.

Enter title in bold, with all first words capitalized, and without a reference number
Design	Objective terms describing the type of study (randomized, uncontrolled, retrospective, placebo-controlled, cross-over, etc.); N= (total subjects)
Objective	State the objective (purpose) of the study using the author’s language(usually beginning with “To” and without a period, assuming a non-complete sentence)
Study Groups	Only the separate groups and their cohort number (n) should be listed. You can describe more details of the cohorts in the methods section so this section can stay very succinct.
Inclusion Criteria	Include relevant inclusion criteria (not a comprehensive list).
Exclusion Criteria	Include relevant exclusion criteria (not a comprehensive list).
Methods	This is our most important section. Data collection and any other information needed to understand the results is presented. Any loose ends from all other sections are tied up here, as concisely as possible.
Duration	Include the duration of the trial as a whole, as well as the duration of the interventions.
Outcome Measures	If the primary outcome measure isn’t explicit from the study, all outcome measures applicable to the inquiry can be listed in this section. If the primary outcome measure is explicit, then make separate sections for ‘Primary’ and ‘Secondary’ Outcome Measures. All outcome measures listed should correlate directly/exactly with the results presented later.
Baseline Characteristics		A	B
	Age, years
	Female
	White
	---
	Include relevant baseline characteristics that will provide a general (big picture) view of the patients in the study.
Results	Endpoint	A	B	p-Value
	----
	----
	All results listed should correlate directly/exactly with the outcome measures presented previously.Results that do not have to do with the inquiry should not be included; just the stated outcomes need corresponding results. Tables are encouraged to display the most info using the least space/words.
Adverse Events	Common Adverse Events: (or those deemed frequent; if not listed in study, use N/A or “Not disclosed”)
	Serious Adverse Events: (or those deemed high risk; if not listed in study, use N/A or “Not disclosed”)
	Percentage that Discontinued due to Adverse Events: (if not listed in study, use N/A or “Not disclosed”)
Study Author Conclusions	Copy and paste the author’s conclusions on the question at hand, using full sentences. Don’t include any conclusions that don’t correspond to results we list.
InpharmD Researcher Critique	As the expert, add 1-2 sentences on strengths, weaknesses, and takeaways from this study. Focus on insight as “more research is needed” is obvious.